DGIdb - BRAF Gene Record

BRAF 673 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

673
B-RAF PROTO-ONCOGENE, SERINE/THREONINE KINASE
BRAF
B-RAF1
B-raf
BRAF1
NS7
RAFB1
164757
1097
ENSG00000157764
OTTHUMG00000157457
P15056
PA25408
v-raf murine sarcoma viral oncogene homolog B1
B-RAF PROTO-ONCOGENE SERINE/THREONINE-PROTEIN KINASE (EC 2.7.1.37) (P94) (V-RAF MURINE SARCOMA VIRAL ONCOGENE HOMOLOG B1). [SOURCE:UNIPROT/SWISSPROT;ACC:P15056]
p94
Proto-oncogene B-Raf
Serine/threonine-protein kinase B-raf
TTDS00346
B-RAF PROTEIN
BRAF SERINE/THREONINE KINASE
BRAF(V599E)
B-RAF PROTO-ONCOGENE SERINE/THREONINE-PROTEIN KINASE
1943
NP_004324
NM_004333
5
BE0000634
BRAF1_HUMAN
BRAF_HUMAN
RAF

Gene Info:

Target Class	Enzymes
Target Subclass	EC:2.7.11.1
Has Variant Annotation	false
Is VIP	false
Human Readable Name	DRUGGABLE GENOME
Gene Biotype	PROTEIN_CODING"
Human Readable Name	SERINE THREONINE KINASE
GuideToPharmacology Gene Category Name	RAF family
GuideToPharmacology Gene Category ID	610
GuideToPharmacology Gene Type	enzyme
Target Subclass	2.7.11.1
Target Main Class	Enzymes
CancerCommons Reported Gene Name	BRAF (V660) E/K
CancerCommons Reported Gene Name	BRAF
CancerCommons Reported Gene Name	Pan-RAF
CancerCommons Reported Gene Name	BRAF V600E
Interpro Short Name	Ser-Thr/Tyr_kinase_cat_dom
Interpro Name	Serine-threonine/tyrosine-protein kinase catalytic domain
Uniprot Evidence	1: Evidence at protein level
Interpro Acc	IPR001245
Uniprot Status	Swiss-Prot
Interpro Type	Domain
Human Readable Name	KINASE
Source Reported Gene Name	BRAF
Gene Category	CLINICALLY ACTIONABLE

(25 More Sources)

Publications:

Peng et al., 2016, Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy., Cancer Discov
Grisham et al., 2015, Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer., J. Clin. Oncol.
Peng et al., 2015, Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers., Cancer Cell
Kirkwood et al., 2012, Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma., Clin. Cancer Res.
Olow et al., 2016, BRAF Status in Personalizing Treatment Approaches for Pediatric Gliomas., Clin. Cancer Res.
Emery et al., 2009, MEK1 mutations confer resistance to MEK and B-RAF inhibition., Proc. Natl. Acad. Sci. U.S.A.
Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.
Beadnell et al., 2016, The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer., Mol. Cancer Ther.
Friedman et al., 2015, Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment., PLoS ONE
Beloueche-Babari et al., 2013, Acute tumour response to the MEK1/2 inhibitor selumetinib (AZD6244, ARRY-142886) evaluated by non-invasive diffusion-weighted MRI., Br. J. Cancer
Narita et al., 2014, Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib-resistant melanoma harboring the MEK1-C121S mutation in a preclinical model., Mol. Cancer Ther.
Nikolaev et al., 2011, Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma., Nat. Genet.
Sweetlove et al., 2015, Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth., Front Oncol
McNew et al., 2016, MEK and TAK1 Regulate Apoptosis in Colon Cancer Cells with KRAS-Dependent Activation of Proinflammatory Signaling., Mol. Cancer Res.
Ho et al., 2013, Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer., N. Engl. J. Med.
Whittaker et al., 2015, Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors., Mol. Cancer Ther.
Bonnevaux et al., 2016, Concomitant Inhibition of PI3Kβ and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kβ-Selective Inhibitor., Mol. Cancer Ther.
Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov
Tang et al., 2015, BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers., Mol. Cancer Ther.
James et al., 2012, CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity., Mol. Cancer Ther.
Su et al., 2012, RAF265 inhibits the growth of advanced human melanoma tumors., Clin. Cancer Res.
Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med
Corcoran et al., 2015, Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer., J. Clin. Oncol.
Silen et al., 1975, Acid-base balance in amphibian gastric mucosa., Am. J. Physiol.
Sakaguchi et al., 1976, Microbiological oxidation of synthetic chalcocite and covellite by Thiobacillus ferrooxidans., Appl. Environ. Microbiol.
Rudin et al., 2013, Molecular characterization of acquired resistance to the BRAF inhibitor dabrafenib in a patient with BRAF-mutant non-small-cell lung cancer., J Thorac Oncol
Falchook et al., 2012, Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial., Lancet
Bland et al., 1976, Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial., Am. J. Obstet. Gynecol.
Fioravanti et al., 1976, Pyridine nucleotide transhydrogenases of parasitic helminths., Arch. Biochem. Biophys.
Poole-Wilson et al., 1975, Effect of pH on ionic exchange and function in rat and rabbit myocardium., Am. J. Physiol.
Garner et al., 1975, Effect of pH on substrate and inhibitor kinetic constants of human liver alanine aminopeptidase. Evidence for two ionizable active center groups., Biochemistry
Flaherty et al., 2010, Inhibition of mutated, activated BRAF in metastatic melanoma., N. Engl. J. Med.
Kim et al., 2013, Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation., Thyroid
Planchard et al., 2016, Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial., Lancet Oncol.
Falchook et al., 2013, BRAF mutant gastrointestinal stromal tumor: first report of regression with BRAF inhibitor dabrafenib (GSK2118436) and whole exomic sequencing for analysis of acquired resistance., Oncotarget
Gibney et al., 2013, Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies., Expert Opin Drug Metab Toxicol
Gautschi et al., 2012, A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib., J Thorac Oncol
Myall et al., 2016, Long-Term Survival of a Patient With Non-Small-Cell Lung Cancer Harboring a V600E Mutation in the BRAF Oncogene., Clin Lung Cancer
Schmid et al., 2015, Response to dabrafenib after progression on vemurafenib in a patient with advanced BRAF V600E-mutant bronchial adenocarcinoma., Lung Cancer
Hyman et al., 2015, Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations., N. Engl. J. Med.
Peters et al., 2013, Dramatic response induced by vemurafenib in a BRAF V600E-mutated lung adenocarcinoma., J. Clin. Oncol.
Gautschi et al., 2015, Targeted Therapy for Patients with BRAF-Mutant Lung Cancer: Results from the European EURAF Cohort., J Thorac Oncol
Robinson et al., 2014, BRAF V600E-mutated lung adenocarcinoma with metastases to the brain responding to treatment with vemurafenib., Lung Cancer
McGettigan, 2014, Dabrafenib: A New Therapy for Use in BRAF-Mutated Metastatic Melanoma., J Adv Pract Oncol
Laurent-Puig et al., 2009, Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer., J. Clin. Oncol.
De Roock et al., 2010, Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis., Lancet Oncol.
Di Nicolantonio et al., 2008, Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer., J. Clin. Oncol.
Huang et al., 2013, B-Raf and the inhibitors: from bench to bedside., J Hematol Oncol
Corcoran et al., 2012, EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib., Cancer Discov
Flaherty et al., 2012, Improved survival with MEK inhibition in BRAF-mutated melanoma., N. Engl. J. Med.
Planchard et al., 2016, Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial., Lancet Oncol.
Hauschild et al., 2012, Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial., Lancet
Wright et al., 2013, Trametinib: first global approval., Drugs
Larkin et al., 2014, Combined vemurafenib and cobimetinib in BRAF-mutated melanoma., N. Engl. J. Med.
Johnson et al., 2014, Combined BRAF (Dabrafenib) and MEK inhibition (Trametinib) in patients with BRAFV600-mutant melanoma experiencing progression with single-agent BRAF inhibitor., J. Clin. Oncol.
Robert et al., 2015, Improved overall survival in melanoma with combined dabrafenib and trametinib., N. Engl. J. Med.
Long et al., 2012, Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial., Lancet Oncol.
Ascierto et al., 2013, Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma., J. Clin. Oncol.
Long et al., 2014, Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma., N. Engl. J. Med.
McArthur et al., 2014, Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study., Lancet Oncol.
Flaherty et al., 2012, Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations., N. Engl. J. Med.
Ponti et al., 2013, The somatic affairs of BRAF: tailored therapies for advanced malignant melanoma and orphan non-V600E (V600R-M) mutations., J. Clin. Pathol.
Menzies et al., 2014, Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma., Clin. Cancer Res.
Klempner et al., 2016, BRAFV600E Mutations in High-Grade Colorectal Neuroendocrine Tumors May Predict Responsiveness to BRAF-MEK Combination Therapy., Cancer Discov
Ponti et al., 2012, Overwhelming response to Dabrafenib in a patient with double BRAF mutation (V600E; V600M) metastatic malignant melanoma., J Hematol Oncol
Ahronian et al., 2015, Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations., Cancer Discov

Karoulia et al., 2016, An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling., Cancer Cell
Carlino et al., 2015, Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic melanoma patients., Clin. Cancer Res.
Gibson et al., 2017, Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer., Clin. Cancer Res.
Greger et al., 2012, Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations., Mol. Cancer Ther.
Hirschi et al., 2014, Genetic targeting of B-RafV600E affects survival and proliferation and identifies selective agents against BRAF-mutant colorectal cancer cells., Mol. Cancer
Schreuer et al., 2017, Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAF(V600)-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial., Lancet Oncol.
Drobysheva et al., 2017, Targeted MAPK Pathway Inhibitors in Patients With Disseminated Pilocytic Astrocytomas., J Natl Compr Canc Netw
Agarwal et al., 2016, Response to Targeted Therapy in BRAF Mutant Anaplastic Thyroid Cancer., J Natl Compr Canc Netw
Wagle et al., 2014, MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition., Cancer Discov
Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov
Long GV et al., 2017 Sep 10, Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma., N Engl J Med
Casadevall et al., 2016, Dabrafenib in an elderly patient with metastatic melanoma and BRAF V600R mutation: a case report., J Med Case Rep
Chen et al., 2016, Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120., Cancer Discov
2016, Triple Therapy Improves Colorectal Cancer Response., Cancer Discov
Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.
Shen et al., 2016, Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma., Nat. Med.
Long et al., 2016, Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib., J. Clin. Oncol.
Lu et al., 2017, Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer., Cancer Res.
Davies et al., 2002, Mutations of the BRAF gene in human cancer., Nature
Naoki et al., 2002, Missense mutations of the BRAF gene in human lung adenocarcinoma., Cancer Res.
Paik et al., 2011, Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations., J. Clin. Oncol.
Ohashi et al., 2012, Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1., Proc. Natl. Acad. Sci. U.S.A.
Rowland et al., 2015, Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer., Br. J. Cancer
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Hatzivassiliou et al., 2013, Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers., Nature
Falchook et al., 2012, Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial., Lancet Oncol.
Kurman et al., 2011, Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm., Hum. Pathol.
Coffee et al., 2013, Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer., Clin. Cancer Res.
Wan et al., 2004, Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF., Cell
Howell et al., 2011, Both BRAF V600E mutation and older age (≥ 65 years) are associated with recurrent papillary thyroid cancer., Ann. Surg. Oncol.
Walczyk et al., 2014, The BRAF(V600E) mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?, Clin. Endocrinol. (Oxf)
De Roock et al., 2011, KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer., Lancet Oncol.
Meckbach et al., 2014, BRAF-V600 mutations have no prognostic impact in stage IV melanoma patients treated with monochemotherapy., PLoS ONE
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
Hayes et al., 2012, Phase II efficacy and pharmacogenomic study of Selumetinib (AZD6244; ARRY-142886) in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements., Clin. Cancer Res.
Zecchin et al., 2013, BRAF V600E is a determinant of sensitivity to proteasome inhibitors., Mol. Cancer Ther.
Lam et al., 2010, Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer., J. Clin. Oncol.
He et al., 2014, Prognostic value of the BRAF V600E mutation in papillary thyroid carcinoma., Oncol Lett
Patel et al., 2013, Clinical responses to selumetinib (AZD6244; ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma., Cancer
Sen et al., 2012, Kinase-impaired BRAF mutations in lung cancer confer sensitivity to dasatinib., Sci Transl Med
Morris et al., 2013, Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors., Cancer Discov
Ji et al., 2013, Vemurafenib synergizes with nutlin-3 to deplete survivin and suppresses melanoma viability and tumor growth., Clin. Cancer Res.
Tol et al., 2010, Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab., Eur. J. Cancer
Chapman et al., 2011, Improved survival with vemurafenib in melanoma with BRAF V600E mutation., N. Engl. J. Med.
Dienstmann et al., 2011, BRAF as a target for cancer therapy., Anticancer Agents Med Chem
Rubinstein et al., 2010, Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032., J Transl Med
Andrulis et al., 2013, Targeting the BRAF V600E mutation in multiple myeloma., Cancer Discov
Crescenzi et al., 2014, Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers., Horm. Metab. Res.
Sarker et al., 2015, First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors., Clin. Cancer Res.
Boulalas et al., Mutational analysis of the BRAF gene in transitional cell carcinoma of the bladder., Int. J. Biol. Markers
Prahallad et al., 2012, Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR., Nature
Gandhi et al., 2009, Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines., PLoS ONE
Jalili et al., 2012, Dual suppression of the cyclin-dependent kinase inhibitors CDKN2C and CDKN1A in human melanoma., J. Natl. Cancer Inst.
Nissan et al., 2014, Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence., Cancer Res.
Cardarella et al., 2013, Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer., Clin. Cancer Res.
Paraiso et al., 2012, The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms., Clin. Cancer Res.
Kloos et al., 2009, Phase II trial of sorafenib in metastatic thyroid cancer., J. Clin. Oncol.
Agaimy et al., 2009, V600E BRAF mutations are alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours., J. Clin. Pathol.
Faber et al., 2014, mTOR inhibition specifically sensitizes colorectal cancers with KRAS or BRAF mutations to BCL-2/BCL-XL inhibition by suppressing MCL-1., Cancer Discov
Tejpar et al., 2010, Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery., Oncologist
Xing et al., 2014, BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence., J. Clin. Oncol.
Penna et al., 2016, Primary cross-resistance to BRAFV600E-, MEK1/2- and PI3K/mTOR-specific inhibitors in BRAF-mutant melanoma cells counteracted by dual pathway blockade., Oncotarget
Haldar et al., 2011, Epidermal growth factor receptor blockers for the treatment of ovarian cancer., Cochrane Database Syst Rev
De Roock et al., 2009, Clinical biomarkers in oncology: focus on colorectal cancer., Mol Diagn Ther
Mao et al., 2011, BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis., Mol. Biol. Rep.
Pratilas et al., 2008, Genetic predictors of MEK dependence in non-small cell lung cancer., Cancer Res.
Nagore et al., 2014, Prognostic value of BRAF mutations in localized cutaneous melanoma., J. Am. Acad. Dermatol.
Peeters et al., 2013, Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer., Clin. Cancer Res.
Huillard et al., 2012, Cooperative interactions of BRAFV600E kinase and CDKN2A locus deficiency in pediatric malignant astrocytoma as a basis for rational therapy., Proc. Natl. Acad. Sci. U.S.A.
Nakayama et al., 2008, KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer., Br. J. Cancer
Chen et al., 2014, BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis., PLoS ONE
Mao et al., 2013, Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents., Clin. Cancer Res.
Lovly et al., 2012, Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials., PLoS ONE
Rizzo et al., 2010, Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?, Cancer Treat. Rev.
Gupta-Abramson et al., 2008, Phase II trial of sorafenib in advanced thyroid cancer., J. Clin. Oncol.
Brose et al., 2002, BRAF and RAS mutations in human lung cancer and melanoma., Cancer Res.
Sosman et al., 2012, Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib., N. Engl. J. Med.
Tiacci et al., 2011, BRAF mutations in hairy-cell leukemia., N. Engl. J. Med.
Villanueva et al., 2010, Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K., Cancer Cell
Yang et al., 2012, Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer., Cancer Res.
Maldonado et al., 2003, Determinants of BRAF mutations in primary melanomas., J. Natl. Cancer Inst.
Rad et al., 2013, A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention., Cancer Cell
Hoftijzer et al., 2009, Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma., Eur. J. Endocrinol.
Nicolaides et al., 2011, Targeted therapy for BRAFV600E malignant astrocytoma., Clin. Cancer Res.
Dienstmann et al., 2015, Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors., Cancer Discov
Hoeflich et al., 2009, Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression., Cancer Res.
Dahlman et al., 2012, BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors., Cancer Discov
Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.
Tsai et al., 2008, Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity., Proc. Natl. Acad. Sci. U.S.A.
Lerner et al., 2015, Targeting a Plk1-Controlled Polarity Checkpoint in Therapy-Resistant Glioblastoma-Propagating Cells., Cancer Res.
Vinik et al., 2016, Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial., Target Oncol
Frederick et al., 2014, Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics., PLoS ONE
Girotti et al., 2013, Inhibiting EGF receptor or SRC family kinase signaling overcomes BRAF inhibitor resistance in melanoma., Cancer Discov
Wagle et al., 2011, Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling., J. Clin. Oncol.
Basile et al., 2014, Inhibition of mutant BRAF splice variant signaling by next-generation, selective RAF inhibitors., Pigment Cell Melanoma Res
Okimoto RA et al., 2016 Nov 22, Preclinical efficacy of a RAF inhibitor that evades paradoxical MAPK pathway activation in protein kinase BRAF-mutant lung cancer., Proc Natl Acad Sci U S A
Napolitano et al., 2015, Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab., Clin. Cancer Res.
Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer
Wilhelm et al., 2011, Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity., Int. J. Cancer
Kaul et al., 2012, Pediatric glioma-associated KIAA1549:BRAF expression regulates neuroglial cell growth in a cell type-specific and mTOR-dependent manner., Genes Dev.
Iyer et al., 2010, Sorafenib: a clinical and pharmacologic review., Expert Opin Pharmacother
Kwitkowski et al., 2010, FDA approval summary: temsirolimus as treatment for advanced renal cell carcinoma., Oncologist
White et al., 2015, The discovery and development of sorafenib for the treatment of thyroid cancer., Expert Opin Drug Discov
Wilhelm et al., 2004, BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis., Cancer Res.
Subbiah et al., 2014, Targeted therapy by combined inhibition of the RAF and mTOR kinases in malignant spindle cell neoplasm harboring the KIAA1549-BRAF fusion protein., J Hematol Oncol

Palanisamy et al., 2010, Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma., Nat. Med.
Nakaoku et al., 2014, Druggable oncogene fusions in invasive mucinous lung adenocarcinoma., Clin. Cancer Res.
Eisen et al., 2006, Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis., Br. J. Cancer
Haluska et al., 2006, Therapeutic targets in melanoma: map kinase pathway., Curr Oncol Rep
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Kim et al., 2007, Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice., Mol. Cancer Ther.
Flaherty, 2006, Chemotherapy and targeted therapy combinations in advanced melanoma., Clin. Cancer Res.
Lu et al., 2010, Sorafenib induces growth inhibition and apoptosis of human chondrosarcoma cells by blocking the RAF/ERK/MEK pathway., J Surg Oncol
Casadei Gardini et al., 2016, Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report., BMC Cancer
Mangana et al., 2012, Sorafenib in melanoma., Expert Opin Investig Drugs
Al-Marrawi et al., 2013, Off-label use of cetuximab plus sorafenib and panitumumab plus regorafenib to personalize therapy for a patient with V600E BRAF-mutant metastatic colon cancer., Cancer Biol. Ther.
Bardelli et al., 2012, The road to resistance: EGFR mutation and cetuximab., Nat. Med.
Smalley et al., 2009, CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations., Oncogene
Bentivegna et al., 2008, Rapid identification of somatic mutations in colorectal and breast cancer tissues using mismatch repair detection (MRD)., Hum. Mutat.
Dietrich et al., 2012, BRAF inhibition in refractory hairy-cell leukemia., N. Engl. J. Med.
Whittaker et al., 2013, A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition., Cancer Discov
Savarese et al., beta-Adrenergic receptor decrease in diabetic rat hearts., Life Sci.
Jordan et al., 2012, Vemurafenib for the treatment of melanoma., Expert Opin Pharmacother
Ali et al., 2014, Extended Antitumor Response of a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib., Case Rep Oncol
Brose et al., 2016, Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial., Lancet Oncol.
Sharman et al., 2014, Vemurafenib response in 2 patients with posttransplant refractory BRAF V600E-mutated multiple myeloma., Clin Lymphoma Myeloma Leuk
Hong et al., 2016, Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation., Cancer Discov
Hutchinson et al., 2013, BRAF fusions define a distinct molecular subset of melanomas with potential sensitivity to MEK inhibition., Clin. Cancer Res.
Bahadoran et al., 2013, Major clinical response to a BRAF inhibitor in a patient with a BRAF L597R-mutated melanoma., J. Clin. Oncol.
Sahadudheen et al., 2016, Long Term Survival and Continued Complete Response of Vemurafenib in a Metastatic Melanoma Patient with BRAF V600K Mutation., Case Rep Oncol Med
Wagenaar et al., 2014, Resistance to vemurafenib resulting from a novel mutation in the BRAFV600E kinase domain., Pigment Cell Melanoma Res
Hoogstraat et al., 2015, Detailed imaging and genetic analysis reveal a secondary BRAF(L505H) resistance mutation and extensive intrapatient heterogeneity in metastatic BRAF mutant melanoma patients treated with vemurafenib., Pigment Cell Melanoma Res
Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature
Choi et al., 2014, Identification of PLX4032-resistance mechanisms and implications for novel RAF inhibitors., Pigment Cell Melanoma Res
Yao et al., 2015, BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms that Determine Their Sensitivity to Pharmacologic Inhibition., Cancer Cell
Nazarian et al., 2010, Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation., Nature
Tiacci et al., 2015, Targeting Mutant BRAF in Relapsed or Refractory Hairy-Cell Leukemia., N. Engl. J. Med.
Lin et al., 2015, The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies., Nat. Genet.
Peh et al., 2016, The Combination of Vemurafenib and Procaspase-3 Activation Is Synergistic in Mutant BRAF Melanomas., Mol. Cancer Ther.
Yaeger et al., 2015, Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic colorectal cancer patients., Clin. Cancer Res.
Montero-Conde et al., 2013, Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF-mutant thyroid carcinomas., Cancer Discov
Kirouac et al., 2017, Clinical responses to ERK inhibition in BRAF(V600E)-mutant colorectal cancer predicted using a computational model., NPJ Syst Biol Appl
Banerjee et al., 2016, A Rare Finding of a BRAF Mutation in Renal Cell Carcinoma with Response to BRAF-Directed Targeted Therapy., Cureus
Kopetz et al., 2015, Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer., J. Clin. Oncol.
Feng et al., 2015, SBI-0640756 Attenuates the Growth of Clinically Unresponsive Melanomas by Disrupting the eIF4F Translation Initiation Complex., Cancer Res.
Feng et al., 2016, A Novel Plant Sesquiterpene Lactone Derivative, DETD-35, Suppresses BRAFV600E Mutant Melanoma Growth and Overcomes Acquired Vemurafenib Resistance in Mice., Mol. Cancer Ther.
Connolly et al., 2014, Anticancer activity of combination targeted therapy using cetuximab plus vemurafenib for refractory BRAF (V600E)-mutant metastatic colorectal carcinoma., Curr Oncol
Mok et al., 2015, Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition., BMC Cancer
Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell
Zick et al., 2017, Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients., Medicine (Baltimore)
Gautschi et al., 2013, Lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib., Lung Cancer
Joshi et al., 2015, Trametinib with or without vemurafenib in BRAF mutated non-small cell lung cancer., PLoS ONE
Kordes et al., 2016, Cooperation of BRAF(F595L) and mutant HRAS in histiocytic sarcoma provides new insights into oncogenic BRAF signaling., Leukemia
Kotschy et al., 2016, The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models., Nature
Budina-Kolomets et al., 2016, HSP70 Inhibition Limits FAK-Dependent Invasion and Enhances the Response to Melanoma Treatment with BRAF Inhibitors., Cancer Res.
Kim et al., 2013, Phase II study of the MEK1/MEK2 inhibitor Trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor., J. Clin. Oncol.
Jing et al., 2012, Comprehensive predictive biomarker analysis for MEK inhibitor GSK1120212., Mol. Cancer Ther.
Bowyer et al., 2014, Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma., Melanoma Res.
Ross et al., 2016, The distribution of BRAF gene fusions in solid tumors and response to targeted therapy., Int. J. Cancer
Teh et al., 2016, An In Vivo Reporter to Quantitatively and Temporally Analyze the Effects of CDK4/6 Inhibitor-Based Therapies in Melanoma., Cancer Res.
Waizenegger et al., 2016, A Novel RAF Kinase Inhibitor with DFG-Out-Binding Mode: High Efficacy in BRAF-Mutant Tumor Xenograft Models in the Absence of Normal Tissue Hyperproliferation., Mol. Cancer Ther.
Lange et al., 2014, Biological and molecular effects of small molecule kinase inhibitors on low-passage human colorectal cancer cell lines., Biomed Res Int
Yu et al., 2015, Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092., PLoS ONE
Ziemke et al., 2016, Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy That Cotargets MEK and CDK4/6., Clin. Cancer Res.
Marconcini et al., 2017, Metastatic BRAF K601E-mutated melanoma reaches complete response to MEK inhibitor trametinib administered for over 36 months., Exp Hematol Oncol
Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature
Heidorn et al., 2010, Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF., Cell
Müller-Gärtner et al., 1989, [Long-term results following surgery or radioiodine treatment of solitary autonomous adenoma of the thyroid gland]., Chirurg
Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.
van Geel et al., 2017, A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer., Cancer Discov
Tripathy et al., 2017, Ribociclib (LEE011): Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors., Clin. Cancer Res.
Niessner et al., 2016, PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo., Clin. Cancer Res.
Hechtman et al., 2015, AKT1 E17K in Colorectal Carcinoma Is Associated with BRAF V600E but Not MSI-H Status: A Clinicopathologic Comparison to PIK3CA Helical and Kinase Domain Mutants., Mol. Cancer Res.
Ciardiello et al., 2016, Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): a randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX., Ann. Oncol.
Montagut et al., 2012, Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer., Nat. Med.
Ascierto et al., 2013, MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study., Lancet Oncol.
Bendell et al., 2017, A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor., Br. J. Cancer
Hoeflich et al., 2012, Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition., Cancer Res.
Janku et al., 2011, PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors., Mol. Cancer Ther.
Solit et al., 2006, BRAF mutation predicts sensitivity to MEK inhibition., Nature
García-García et al., 2015, MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer., Clin. Cancer Res.
Acquaviva et al., 2014, Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespib., Mol. Cancer Ther.
Lieu et al., 2015, Antitumor activity of a potent MEK inhibitor, TAK-733, against colorectal cancer cell lines and patient derived xenografts., Oncotarget
Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov
Hong et al., 2015, Phase I Dose-Escalation Study of the Multikinase Inhibitor Lenvatinib in Patients with Advanced Solid Tumors and in an Expanded Cohort of Patients with Melanoma., Clin. Cancer Res.
Mohseni et al., 2010, PIK3CA and KRAS mutations predict for response to everolimus therapy: now that's RAD001., J. Clin. Invest.
Di Nicolantonio et al., 2010, Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus., J. Clin. Invest.
Aung et al., 2016, Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer., Cold Spring Harb Mol Case Stud
Herath et al., 2016, The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis., Mol. Cancer Ther.
Dietlein et al., 2015, A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer., Cell
LaBonte et al., 2011, The dual EGFR/HER2 inhibitor lapatinib synergistically enhances the antitumor activity of the histone deacetylase inhibitor panobinostat in colorectal cancer models., Cancer Res.
Smith et al., 2015, The HSP90 inhibitor ganetespib potentiates the antitumor activity of EGFR tyrosine kinase inhibition in mutant and wild-type non-small cell lung cancer., Target Oncol
Byron et al., 2012, Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status., Mol. Cancer
Ahmed et al., 2013, Epigenetic and genetic features of 24 colon cancer cell lines., Oncogenesis
Mallon et al., 2011, Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor., Clin. Cancer Res.
Hollestelle et al., 2007, Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines., Mol. Cancer Res.
Nakanishi et al., 2015, ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor., Mol. Cancer Ther.
Iverson et al., 2009, RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer., Cancer Res.
Hassan et al., 2014, Catalytic mTOR inhibitors can overcome intrinsic and acquired resistance to allosteric mTOR inhibitors., Oncotarget
Foster et al., 2015, The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models., Mol. Cancer Ther.
Anderson et al., 2016, PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation., Sci Transl Med
Otani et al., 2015, TAE226, a Bis-Anilino Pyrimidine Compound, Inhibits the EGFR-Mutant Kinase Including T790M Mutant to Show Anti-Tumor Effect on EGFR-Mutant Non-Small Cell Lung Cancer Cells., PLoS ONE
Garnett et al., 2012, Systematic identification of genomic markers of drug sensitivity in cancer cells., Nature
Woan et al., 2015, Targeting histone deacetylase 6 mediates a dual anti-melanoma effect: Enhanced antitumor immunity and impaired cell proliferation., Mol Oncol
Tanaka et al., 2011, The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations., Clin. Cancer Res.

BGB-283 BRAF

Interaction Types:

inhibitor

Interaction Info:

Details of the Assay for Interaction Inhibition of wild type BRAF kinase domain (aa416-766)

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

Tang et al., 2015, BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers., Mol. Cancer Ther.
CEP-32496 BRAF

Interaction Types:

inhibitor

Interaction Info:

Details of the Assay for Interaction Inhibition of wild type BRAF activity.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

James et al., 2012, CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity., Mol. Cancer Ther.

CHIR-265 BRAF

Interaction Types:

inhibitor

Interaction Info:

Trial Name CHIR-265

Novel drug target Established target

Specific Action of the Ligand Inhibition

Publications:

Su et al., 2012, RAF265 inhibits the growth of advanced human melanoma tumors., Clin. Cancer Res.

Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med

CHEMBL525191 BRAF

Interaction Types:

inhibitor

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Preclinical - Pdx

Publications:

Hoeflich et al., 2009, Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression., Cancer Res.

Coffee et al., 2013, Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer., Clin. Cancer Res.

LY-3009120 BRAF

Interaction Types:

inhibitor

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:

Chen et al., 2016, Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120., Cancer Discov

Peng et al., 2015, Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers., Cancer Cell

Dahlman et al., 2012, BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors., Cancer Discov

PLX-4720 BRAF

Interaction Types:

inhibitor

Interaction Info:

Drug family BRAF inhibitor

Alteration BRAF:V600E

Specific Action of the Ligand Inhibition

Publications:

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

Rad et al., 2013, A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention., Cancer Cell

Tsai et al., 2008, Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity., Proc. Natl. Acad. Sci. U.S.A.

PLX-8394 BRAF

Interaction Types:

inhibitor

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:

Basile et al., 2014, Inhibition of mutant BRAF splice variant signaling by next-generation, selective RAF inhibitors., Pigment Cell Melanoma Res

Okimoto RA et al., 2016 Nov 22, Preclinical efficacy of a RAF inhibitor that evades paradoxical MAPK pathway activation in protein kinase BRAF-mutant lung cancer., Proc Natl Acad Sci U S A

REGORAFENIB BRAF

Interaction Types:

inhibitor

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Publications:

Napolitano et al., 2015, Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab., Clin. Cancer Res.

Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer

Wilhelm et al., 2011, Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity., Int. J. Cancer

SB590885 BRAF

Interaction Types:

inhibitor

Interaction Info:

Details of the Assay for Interaction In a cell-free assay

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med

Karoulia et al., 2016, An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling., Cancer Cell

ENCORAFENIB BRAF

Interaction Types:

inhibitor

Interaction Info:

Notes

combination therapy LGX818 + Cetuximab + BYL719

Indication/Tumor Type colorectal cancer

Publications:

Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.

Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.

van Geel et al., 2017, A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer., Cancer Discov

DASATINIB BRAF

Interaction Types:

inhibitor

Interaction Info:

Drug family BCR-ABL inhibitor 2nd gen

Alteration BRAF:Y472C

Alteration BRAF:G466V

Publications:

Pratilas et al., 2008, Genetic predictors of MEK dependence in non-small cell lung cancer., Cancer Res.

Cardarella et al., 2013, Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer., Clin. Cancer Res.

Davies et al., 2002, Mutations of the BRAF gene in human cancer., Nature

CHEMBL373011 BRAF

Interaction Types:

inhibitor

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:
XL-281 BRAF

Interaction Types:

inhibitor

Interaction Info:

Trial Name XL281

Novel drug target Established target

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Publications:
ARQ-736 BRAF

Interaction Types:

inhibitor

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Notes Targets wildtype BRAF and BRAF with V600E mutation

Publications:
RG-7256 BRAF

Interaction Types:

inhibitor

Interaction Info:

Reported Cancer Type Melanoma

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Publications:
CHEMBL523411 BRAF

Interaction Types:

inhibitor

Interaction Info:

Trial Name GSK2118436

Novel drug target Established target

Publications:
DABRAFENIB MESYLATE BRAF

Interaction Types:

inhibitor

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Publications:
MLN-2480 BRAF

Interaction Types:

inhibitor

Interaction Info:

Mechanism of Interaction RAF serine/threonine protein kinase inhibitor

Direct Interaction yes

Indication/Tumor Type Advanced Solid Tumor

Publications:
SORAFENIB TOSYLATE BRAF

Interaction Types:

inhibitor

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Publications:
LGX-806 BRAF

Interaction Types:

inhibitor

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Publications:

DABRAFENIB BRAF

Interaction Types:

inhibitor

Interaction Info:

combination therapy Dabrafenib;Trametinib

Drug family BRAF inhibitor;MEK inhibitor

Alteration BRAF:V600E

Publications:

Corcoran et al., 2015, Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer., J. Clin. Oncol.

Silen et al., 1975, Acid-base balance in amphibian gastric mucosa., Am. J. Physiol.

Sakaguchi et al., 1976, Microbiological oxidation of synthetic chalcocite and covellite by Thiobacillus ferrooxidans., Appl. Environ. Microbiol.

SORAFENIB BRAF

Interaction Types:

inhibitor

Interaction Info:

combination therapy Sorafenib + Temsirolimus

Trial Name Nexavar

Novel drug target Established target

Publications:

Kaul et al., 2012, Pediatric glioma-associated KIAA1549:BRAF expression regulates neuroglial cell growth in a cell type-specific and mTOR-dependent manner., Genes Dev.

Iyer et al., 2010, Sorafenib: a clinical and pharmacologic review., Expert Opin Pharmacother

Kwitkowski et al., 2010, FDA approval summary: temsirolimus as treatment for advanced renal cell carcinoma., Oncologist

VEMURAFENIB BRAF

Interaction Types:

inhibitor

Interaction Info:

Trial Name PLX4032, RG7204

Novel drug target Established target

Drug family BRAF inhibitor

Publications:

Gautschi et al., 2012, A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib., J Thorac Oncol

Dietrich et al., 2012, BRAF inhibition in refractory hairy-cell leukemia., N. Engl. J. Med.

Andrulis et al., 2013, Targeting the BRAF V600E mutation in multiple myeloma., Cancer Discov

TEMSIROLIMUS BRAF

Interaction Types:

inhibitor

Interaction Info:

combination therapy Bevacizumab + Temsirolimus + Doxil

Indication/Tumor Type ovarian carcinoma

Response Type sensitive

Publications:

Janku et al., 2011, PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors., Mol. Cancer Ther.

Kaul et al., 2012, Pediatric glioma-associated KIAA1549:BRAF expression regulates neuroglial cell growth in a cell type-specific and mTOR-dependent manner., Genes Dev.

Iyer et al., 2010, Sorafenib: a clinical and pharmacologic review., Expert Opin Pharmacother

PEMBROLIZUMAB BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type no benefit

Approval Status Preclinical

Publications:

Peng et al., 2016, Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy., Cancer Discov

SELUMETINIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Selumetinib + Paclitaxel

Drug family MEK inhibitor

Alteration BRAF__.

Publications:

Grisham et al., 2015, Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer., J. Clin. Oncol.

Peng et al., 2015, Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers., Cancer Cell

Kirkwood et al., 2012, Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma., Clin. Cancer Res.

BINIMETINIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Encorafenib + Binimetinib + Cetuximab

combination therapy Binimetinib + BKM120

Indication/Tumor Type melanoma

Publications:

Laurent-Puig et al., 2009, Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer., J. Clin. Oncol.

De Roock et al., 2010, Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis., Lancet Oncol.

Di Nicolantonio et al., 2008, Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer., J. Clin. Oncol.

PD-0325901 BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type resistant

Approval Status Preclinical

Publications:

Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell

Solit et al., 2006, BRAF mutation predicts sensitivity to MEK inhibition., Nature

Lerner et al., 2015, Targeting a Plk1-Controlled Polarity Checkpoint in Therapy-Resistant Glioblastoma-Propagating Cells., Cancer Res.

PIMASERTIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Pimasertib + Sorafenib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer

ALPELISIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Panitumumab;Dabrafenib;BYL719

Drug family EGFR mAb inhibitor;BRAF inhibitor;PI3K inhibitor

Alteration BRAF:V600.

Publications:

Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.

van Geel et al., 2017, A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer., Cancer Discov

Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.

PICTILISIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy GDC0879 + GDC-0941

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Rad et al., 2013, A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention., Cancer Cell

Hoeflich et al., 2009, Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression., Cancer Res.

Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov

GEFITINIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Vemurafenib + Gefitinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Prahallad et al., 2012, Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR., Nature

Corcoran et al., 2012, EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib., Cancer Discov

Girotti et al., 2013, Inhibiting EGF receptor or SRC family kinase signaling overcomes BRAF inhibitor resistance in melanoma., Cancer Discov

DACTOLISIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy BEZ235 + Vemurafenib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Coffee et al., 2013, Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer., Clin. Cancer Res.

Sweetlove et al., 2015, Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth., Front Oncol

IRINOTECAN BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Cetuximab + Irinotecan

Indication/Tumor Type colorectal cancer

Response Type resistant

Publications:

Hong et al., 2016, Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation., Cancer Discov

Hechtman et al., 2015, AKT1 E17K in Colorectal Carcinoma Is Associated with BRAF V600E but Not MSI-H Status: A Clinicopathologic Comparison to PIK3CA Helical and Kinase Domain Mutants., Mol. Cancer Res.

Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature

TAK-733 BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Phase I

Publications:

Dahlman et al., 2012, BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors., Cancer Discov

Acquaviva et al., 2014, Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespib., Mol. Cancer Ther.

Lieu et al., 2015, Antitumor activity of a potent MEK inhibitor, TAK-733, against colorectal cancer cell lines and patient derived xenografts., Oncotarget

NERATINIB BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov

LENVATINIB BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Phase I

Publications:

Hong et al., 2015, Phase I Dose-Escalation Study of the Multikinase Inhibitor Lenvatinib in Patients with Advanced Solid Tumors and in an Expanded Cohort of Patients with Melanoma., Clin. Cancer Res.

BUPARLISIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Binimetinib + BKM120

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Niessner et al., 2016, PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo., Clin. Cancer Res.

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov

PALBOCICLIB BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

Teh et al., 2016, An In Vivo Reporter to Quantitatively and Temporally Analyze the Effects of CDK4/6 Inhibitor-Based Therapies in Melanoma., Cancer Res.

Ziemke et al., 2016, Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy That Cotargets MEK and CDK4/6., Clin. Cancer Res.

EVEROLIMUS BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Everolimus + Selumetinib

Indication/Tumor Type malignant glioma

Response Type predicted – sensitive

Publications:

Olow et al., 2016, BRAF Status in Personalizing Treatment Approaches for Pediatric Gliomas., Clin. Cancer Res.

Gibson et al., 2017, Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer., Clin. Cancer Res.

Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer

IMATINIB BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Guideline

Publications:

Vinik et al., 2016, Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial., Target Oncol

FLUOROURACIL BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Fluorouracil + Leucovorin + Trastuzumab

Indication/Tumor Type rectum adenocarcinoma

Response Type no benefit

Publications:

Aung et al., 2016, Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer., Cold Spring Harb Mol Case Stud

Herath et al., 2016, The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis., Mol. Cancer Ther.

LEUCOVORIN BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Fluorouracil + Leucovorin + Trastuzumab

Indication/Tumor Type rectum adenocarcinoma

Response Type no benefit

Publications:

Aung et al., 2016, Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer., Cold Spring Harb Mol Case Stud
TRASTUZUMAB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Fluorouracil + Leucovorin + Trastuzumab

Indication/Tumor Type rectum adenocarcinoma

Response Type no benefit

Publications:

Aung et al., 2016, Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer., Cold Spring Harb Mol Case Stud
CHEMBL1231206 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy PF3644022 + PF-477736

Indication/Tumor Type lung adenocarcinoma

Response Type predicted – sensitive

Publications:

Dietlein et al., 2015, A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer., Cell
PF-00477736 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy PF3644022 + PF-477736

Indication/Tumor Type lung adenocarcinoma

Response Type predicted – sensitive

Publications:

Dietlein et al., 2015, A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer., Cell

CI-1040 BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical

Publications:

Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med

Emery et al., 2009, MEK1 mutations confer resistance to MEK and B-RAF inhibition., Proc. Natl. Acad. Sci. U.S.A.

Nakayama et al., 2008, KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer., Br. J. Cancer

CHEMBL2204502 BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Paraiso et al., 2012, The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms., Clin. Cancer Res.

LAPATINIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Lapatinib + Panobinostat

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

LaBonte et al., 2011, The dual EGFR/HER2 inhibitor lapatinib synergistically enhances the antitumor activity of the histone deacetylase inhibitor panobinostat in colorectal cancer models., Cancer Res.

Montero-Conde et al., 2013, Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF-mutant thyroid carcinomas., Cancer Discov

PANOBINOSTAT BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Lapatinib + Panobinostat

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

LaBonte et al., 2011, The dual EGFR/HER2 inhibitor lapatinib synergistically enhances the antitumor activity of the histone deacetylase inhibitor panobinostat in colorectal cancer models., Cancer Res.

GANETESPIB BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type skin melanoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Acquaviva et al., 2014, Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespib., Mol. Cancer Ther.

Smith et al., 2015, The HSP90 inhibitor ganetespib potentiates the antitumor activity of EGFR tyrosine kinase inhibition in mutant and wild-type non-small cell lung cancer., Target Oncol

TIVOZANIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy PLX4720 + Tivozanib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Friedman et al., 2015, Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment., PLoS ONE
CHEMBL217354 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Trametinib + TW-37

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Lin et al., 2015, The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies., Nat. Genet.

DOXORUBICIN BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy PLX4720 + Doxorubicin

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Vinik et al., 2016, Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial., Target Oncol

BI-2536 BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type glioblastoma multiforme

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

Lerner et al., 2015, Targeting a Plk1-Controlled Polarity Checkpoint in Therapy-Resistant Glioblastoma-Propagating Cells., Cancer Res.

OMIPALISIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Dabrafenib + GSK2126458

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Greger et al., 2012, Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations., Mol. Cancer Ther.

E-6201 BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Narita et al., 2014, Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib-resistant melanoma harboring the MEK1-C121S mutation in a preclinical model., Mol. Cancer Ther.

Byron et al., 2012, Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status., Mol. Cancer

NAVITOCLAX BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Trametinib + Navitoclax

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Publications:

Lin et al., 2015, The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies., Nat. Genet.

Frederick et al., 2014, Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics., PLoS ONE

Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.

CEDIRANIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Cediranib + Selumetinib + PLX4720

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Friedman et al., 2015, Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment., PLoS ONE

GEDATOLISIB BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type colon cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Ahmed et al., 2013, Epigenetic and genetic features of 24 colon cancer cell lines., Oncogenesis

Mallon et al., 2011, Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor., Clin. Cancer Res.

Hollestelle et al., 2007, Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines., Mol. Cancer Res.

SARACATINIB BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Girotti et al., 2013, Inhibiting EGF receptor or SRC family kinase signaling overcomes BRAF inhibitor resistance in melanoma., Cancer Discov
Ribociclib BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Encorafenib + Ribociclib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Tripathy et al., 2017, Ribociclib (LEE011): Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors., Clin. Cancer Res.

ERLOTINIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Erlotinib + PLX4720

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Vinik et al., 2016, Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial., Target Oncol

Corcoran et al., 2012, EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib., Cancer Discov

Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.

AFATINIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy BI 882370 + Afatinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Waizenegger et al., 2016, A Novel RAF Kinase Inhibitor with DFG-Out-Binding Mode: High Efficacy in BRAF-Mutant Tumor Xenograft Models in the Absence of Normal Tissue Hyperproliferation., Mol. Cancer Ther.

Ro-4987655 BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

Nakanishi et al., 2015, ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor., Mol. Cancer Ther.
Refametinib BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Iverson et al., 2009, RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer., Cancer Res.

VORINOSTAT BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy PLX4720 + Vorinostat

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Vinik et al., 2016, Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial., Target Oncol

OXALIPLATIN BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy DT01 + Fluorouracil + Oxaliplatin

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Herath et al., 2016, The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis., Mol. Cancer Ther.
ARQ-092 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy ARQ092 + Trametinib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Yu et al., 2015, Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092., PLoS ONE

INK-128 BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Hassan et al., 2014, Catalytic mTOR inhibitors can overcome intrinsic and acquired resistance to allosteric mTOR inhibitors., Oncotarget

García-García et al., 2015, MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer., Clin. Cancer Res.

PLX-3397 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy PLX3397 + Vemurafenib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Mok et al., 2015, Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition., BMC Cancer

PILARALISIB (CHEMBL3218575) BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Foster et al., 2015, The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models., Mol. Cancer Ther.

GSK-2636771 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy GSK2636771 + unspecified PD-1 antibody

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Peng et al., 2016, Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy., Cancer Discov

Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.

PHENMETRAZINE BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type no benefit

Approval Status Preclinical

Publications:

Sweetlove et al., 2015, Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth., Front Oncol
ZSTK-474 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Vemurafenib + ZSTK474

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Sweetlove et al., 2015, Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth., Front Oncol
IDELALISIB BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type no benefit

Approval Status Preclinical

Publications:

Sweetlove et al., 2015, Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth., Front Oncol
VENETOCLAX BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Venetoclax + VX-11e

Indication/Tumor Type colorectal cancer

Response Type no benefit

Publications:

Anderson et al., 2016, PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation., Sci Transl Med

CHEMBL458997 BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

Approval Status Preclinical

Publications:

Otani et al., 2015, TAE226, a Bis-Anilino Pyrimidine Compound, Inhibits the EGFR-Mutant Kinase Including T790M Mutant to Show Anti-Tumor Effect on EGFR-Mutant Non-Small Cell Lung Cancer Cells., PLoS ONE

CAPMATINIB BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type collecting duct carcinoma

Response Type sensitive

Approval Status Preclinical - Pdx

Publications:

Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature
AZD-6482 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy AZD6482 + NVP-AEW541

Indication/Tumor Type melanoma

Response Type no benefit

Publications:

Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.
AEW-541 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy AZD6482 + NVP-AEW541

Indication/Tumor Type melanoma

Response Type no benefit

Publications:

Herkert et al., 2016, Maximizing the Efficacy of MAPK-Targeted Treatment in PTENLOF/BRAFMUT Melanoma through PI3K and IGF1R Inhibition., Cancer Res.
OBATOCLAX BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical

Publications:

Garnett et al., 2012, Systematic identification of genomic markers of drug sensitivity in cancer cells., Nature
TUBASTATIN A BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical

Publications:

Woan et al., 2015, Targeting histone deacetylase 6 mediates a dual anti-melanoma effect: Enhanced antitumor immunity and impaired cell proliferation., Mol Oncol
LY-294002 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy E6201 + LY294002

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Byron et al., 2012, Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status., Mol. Cancer
PF-04217903 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy ABT-263 + CGM097 + Dabrafenib + PF-04217903

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., Cancer Res.

SAR-260301 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy SAR260301 + Selumetinib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Bonnevaux et al., 2016, Concomitant Inhibition of PI3Kβ and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kβ-Selective Inhibitor., Mol. Cancer Ther.

UPROSERTIB BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov
MK-2206 BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy MK2206 + Trametinib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov
BEVACIZUMAB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Bevacizumab + Temsirolimus + Doxil

Indication/Tumor Type ovarian carcinoma

Response Type sensitive

Publications:

Janku et al., 2011, PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors., Mol. Cancer Ther.
PA-799 BRAF

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type breast cancer

Response Type decreased response

Approval Status Preclinical - Cell line xenograft

Publications:

Tanaka et al., 2011, The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations., Clin. Cancer Res.
CRIZOTINIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Crizotinib;Vemurafenib

Drug family ALK inhibitor;BRAF inhibitor

Alteration MET:amp;BRAF:V600E

Publications:
Voruciclib BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Vemurafenib + Voruciclib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:
ATEZOLIZUMAB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Atezolizumab + Vemurafenib + Cobimetinib

Indication/Tumor Type melanoma

Response Type sensitive

Publications:
CHEMBL526479 BRAF

Interaction Types:

n/a

Interaction Info:

Publications:

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

TRAMETINIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Dabrafenib;Trametinib

Drug family BRAF inhibitor;MEK inhibitor

Alteration BRAF:V600E

Publications:

Corcoran et al., 2015, Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer., J. Clin. Oncol.

Silen et al., 1975, Acid-base balance in amphibian gastric mucosa., Am. J. Physiol.

Sakaguchi et al., 1976, Microbiological oxidation of synthetic chalcocite and covellite by Thiobacillus ferrooxidans., Appl. Environ. Microbiol.

PANITUMUMAB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Panitumumab;Dabrafenib;BYL719

Drug family EGFR mAb inhibitor;BRAF inhibitor;PI3K inhibitor

Alteration BRAF:V600.

Publications:

De Roock et al., 2010, Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis., Lancet Oncol.

De Roock et al., 2011, KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer., Lancet Oncol.

Peeters et al., 2013, Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer., Clin. Cancer Res.

CETUXIMAB BRAF

Interaction Types:

n/a

Interaction Info:

Drug family EGFR mAb inhibitor

Alteration BRAF:V600E

combination therapy Dabrafenib + Cetuximab

Publications:

De Roock et al., 2010, Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis., Lancet Oncol.

De Roock et al., 2011, KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer., Lancet Oncol.

Peeters et al., 2013, Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer., Clin. Cancer Res.

COBIMETINIB BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Vemurafenib;Cobimetinib

Drug family BRAF inhibitor;MEK inhibitor

Alteration BRAF:V600E,V600K

Publications:

Hauschild et al., 2012, Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial., Lancet

Wright et al., 2013, Trametinib: first global approval., Drugs

Larkin et al., 2014, Combined vemurafenib and cobimetinib in BRAF-mutated melanoma., N. Engl. J. Med.

PACLITAXEL BRAF

Interaction Types:

n/a

Interaction Info:

combination therapy Selumetinib + Paclitaxel

Publications:

Grisham et al., 2015, Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer., J. Clin. Oncol.
NIVOLUMAB BRAF

Interaction Types:

n/a

Interaction Info:

Publications:

Ensembl: ENSG00000157764
- Version: 90_38
Alternate Names:

BRAF Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING"

Publications:
dGene: 673
- Version: 27-June-2013
Alternate Names:

673 Entrez Gene Id

BRAF Gene Symbol

Gene Info:

Human Readable Name SERINE THREONINE KINASE

Publications:
TdgClinicalTrial: P15056
- Version: January-2014
Alternate Names:

BRAF Gene Symbol

Gene Info:

Target Class Enzymes

Target Subclass EC:2.7.11.1

Publications:

RussLampel: ENSG00000157764

Version: 26-July-2011

Alternate Names:

B-RAF PROTO-ONCOGENE SERINE/THREONINE-PROTEIN KINASE (EC 2.7.1.37) (P94) (V-RAF MURINE SARCOMA VIRAL ONCOGENE HOMOLOG B1). [SOURCE:UNIPROT/SWISSPROT;ACC:P15056] Description

BRAF Display Id

ENSG00000157764 Ensembl Gene Id

Gene Info:

Human Readable Name DRUGGABLE GENOME

Publications:

TEND: P15056
- Version: 01-August-2011
Alternate Names:

673 Entrez Gene Id

BRAF Gene Symbol

P15056 Uniprot Accession

Gene Info:

Target Subclass 2.7.11.1

Target Main Class Enzymes

Publications:
FoundationOneGenes: BRAF
- Version: 20-September-2013
Alternate Names:

673 Entrez Gene ID

Gene Info:

Source Reported Gene Name BRAF

Gene Category CLINICALLY ACTIONABLE

Publications:
CancerCommons: BRAF
- Version: 25-July-2013
Alternate Names:

673 Entrez Gene ID

Gene Info:

CancerCommons Reported Gene Name BRAF (V660) E/K

CancerCommons Reported Gene Name BRAF

CancerCommons Reported Gene Name Pan-RAF

Publications:
HopkinsGroom: P15056
- Version: 11-September-2012
Alternate Names:

BRAF Uniprot Gene Name

P15056 Uniprot Accession

ENSG00000157764 Ensembl Gene Id

Gene Info:

Interpro Short Name Ser-Thr/Tyr_kinase_cat_dom

Interpro Name Serine-threonine/tyrosine-protein kinase catalytic domain

Uniprot Evidence 1: Evidence at protein level

Publications:
GuideToPharmacologyGenes: 1943
- Version: 4-March-2015
Alternate Names:

673 Entrez Gene ID

P15056 SwissProt Accession

NP_004324 RefSeq Protein Accession

Gene Info:

GuideToPharmacology Gene Category Name RAF family

GuideToPharmacology Gene Category ID 610

GuideToPharmacology Gene Type enzyme

Publications:
PharmGKB: PA25408
- Version: 12-July-2012
Alternate Names:

v-raf murine sarcoma viral oncogene homolog B1 Gene Name

ENSG00000157764 Ensembl Gene Id

673 Entrez Gene Id

Gene Info:

Has Variant Annotation false

Is VIP false

Publications:

OncoKB: BRAF

Version: 27-September-2017

Alternate Names:

B-RAF1 OncoKB Gene Synonym

RAFB1 OncoKB Gene Synonym

BRAF1 OncoKB Gene Synonym

Gene Info:

Publications:

Laurent-Puig et al., 2009, Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer., J. Clin. Oncol.

De Roock et al., 2010, Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis., Lancet Oncol.

Di Nicolantonio et al., 2008, Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer., J. Clin. Oncol.

CIViC: BRAF

Version: 27-September-2017

Alternate Names:

5 CIViC Gene ID

673 Entrez Gene ID

Gene Info:

Publications:

Menzies et al., 2014, Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma., Clin. Cancer Res.

Robert et al., 2015, Improved overall survival in melanoma with combined dabrafenib and trametinib., N. Engl. J. Med.

Klempner et al., 2016, BRAFV600E Mutations in High-Grade Colorectal Neuroendocrine Tumors May Predict Responsiveness to BRAF-MEK Combination Therapy., Cancer Discov

CKB: BRAF

Version: 27-September-2017

Alternate Names:

RAFB1 CKB Gene Synonym

NS7 CKB Gene Synonym

BRAF1 CKB Gene Synonym

Gene Info:

Publications:

Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature

Dahlman et al., 2012, BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors., Cancer Discov

DrugBank: BE0000634

Version: 5.0.8

Alternate Names:

ENSG00000157764 Ensembl Gene Id

673 Entrez Gene Id

P15056 UniProt Accession

Gene Info:

Publications:

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

Eisen et al., 2006, Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis., Br. J. Cancer

Haluska et al., 2006, Therapeutic targets in melanoma: map kinase pathway., Curr Oncol Rep

CGI: BRAF

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

Gautschi et al., 2012, A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib., J Thorac Oncol

Dietrich et al., 2012, BRAF inhibition in refractory hairy-cell leukemia., N. Engl. J. Med.

Andrulis et al., 2013, Targeting the BRAF V600E mutation in multiple myeloma., Cancer Discov

DoCM: BRAF

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

Davies et al., 2002, Mutations of the BRAF gene in human cancer., Nature

Gautschi et al., 2012, A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib., J Thorac Oncol

Naoki et al., 2002, Missense mutations of the BRAF gene in human lung adenocarcinoma., Cancer Res.

GuideToPharmacologyInteractions: 1943
- Version: 27-September-2017
Alternate Names:

P15056 UniProtKB ID

B-Raf proto-oncogene, serine/threonine kinase GuideToPharmacology Name

Gene Info:

Publications:
HingoraniCasas: ENSG00000157764
- Version: 31-May-2017
Alternate Names:

BRAF Ensembl Id

ENSG00000157764 Gene Symbol

Gene Info:

Publications:
TALC: BRAF
- Version: 12-May-2016
Alternate Names:

BRAF Gene Symbol

Gene Info:

Publications:
GO: BRAF
- Version: 27-September-2017
Alternate Names:

RAFB1 GO Gene Synonym

BRAF1 GO Gene Synonym

BRAF_HUMAN GO Gene Synonym

Gene Info:

Publications:
TTD: TTDS00346
- Version: 4.3.02 (25-August-2011)
Alternate Names:

v-raf murine sarcoma viral oncogene homolog B1 Gene Synonym

ENSG00000157764 Ensembl Gene Id

673 Entrez Gene Id

Gene Info:

Publications:
MyCancerGenome: BRAF
- Version: 20-Jun-2017
Alternate Names:

RAF MyCancerGenome Reported Gene Name

BRAF MyCancerGenome Reported Gene Name

BRAF MyCancerGenome Gene Symbol

Gene Info:

Publications:
ChemblInteractions: BRAF1
- Version: chembl_23
Alternate Names:

BRAF1 GENE_SYMBOL

v-Raf murine sarcoma viral oncogene homolog B1 UNIPROT

p94 UNIPROT

Gene Info:

Publications:
ClearityFoundationBiomarkers: BRAF
- Version: 26-July-2013
Alternate Names:

Gene Info:

Publications:
ClearityFoundationClinicalTrial: BRAF
- Version: 15-June-2013
Alternate Names:

Gene Info:

Publications:
MyCancerGenomeClinicalTrial: BRAF
- Version: 30-February-2014
Alternate Names:

Gene Info:

Publications:
CarisMolecularIntelligence: BRAF
- Version: 07-October-2015
Alternate Names:

Gene Info:

Publications:
FDA: BRAF
- Version: 15-September-2017
Alternate Names:

Gene Info:

Publications:
MskImpact: BRAF
- Version: May-2015
Alternate Names:

Gene Info:

Publications:

Details of the Assay for Interaction	Inhibition of wild type BRAF kinase domain (aa416-766)
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Details of the Assay for Interaction	Inhibition of wild type BRAF activity.
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Trial Name	CHIR-265
Novel drug target	Established target
Specific Action of the Ligand	Inhibition

Indication/Tumor Type	non-small cell lung carcinoma
Response Type	resistant
Approval Status	Preclinical - Pdx

Drug family	BRAF inhibitor
Alteration	BRAF:V600E
Specific Action of the Ligand	Inhibition

Details of the Assay for Interaction	In a cell-free assay
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Notes
combination therapy	LGX818 + Cetuximab + BYL719
Indication/Tumor Type	colorectal cancer

Drug family	BCR-ABL inhibitor 2nd gen
Alteration	BRAF:Y472C
Alteration	BRAF:G466V

Trial Name	XL281
Novel drug target	Established target
Mechanism of Interaction	Serine/threonine-protein kinase B-raf inhibitor

Mechanism of Interaction	Serine/threonine-protein kinase B-raf inhibitor
Direct Interaction	yes
Notes	Targets wildtype BRAF and BRAF with V600E mutation

Reported Cancer Type	Melanoma
Mechanism of Interaction	Serine/threonine-protein kinase B-raf inhibitor
Direct Interaction	yes

Mechanism of Interaction	RAF serine/threonine protein kinase inhibitor
Direct Interaction	yes
Indication/Tumor Type	Advanced Solid Tumor

combination therapy	Dabrafenib;Trametinib
Drug family	BRAF inhibitor;MEK inhibitor
Alteration	BRAF:V600E

combination therapy	Sorafenib + Temsirolimus
Trial Name	Nexavar
Novel drug target	Established target

Trial Name	PLX4032, RG7204
Novel drug target	Established target
Drug family	BRAF inhibitor

combination therapy	Bevacizumab + Temsirolimus + Doxil
Indication/Tumor Type	ovarian carcinoma
Response Type	sensitive

combination therapy	Selumetinib + Paclitaxel
Drug family	MEK inhibitor
Alteration	BRAF__.

combination therapy	Encorafenib + Binimetinib + Cetuximab
combination therapy	Binimetinib + BKM120
Indication/Tumor Type	melanoma

combination therapy	Pimasertib + Sorafenib
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

combination therapy	Panitumumab;Dabrafenib;BYL719
Drug family	EGFR mAb inhibitor;BRAF inhibitor;PI3K inhibitor
Alteration	BRAF:V600.

BRAF Gene Record

BRAF 673 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

Gene Info:

Publications:

Interaction Types: inhibitor

Interaction Info: Details of the Assay for Interaction Inhibition of wild type BRAF kinase domain (aa416-766) Specific Action of the Ligand Inhibition Endogenous Drug? False

Publications: Tang et al., 2015, BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers., Mol. Cancer Ther.

Interaction Types: inhibitor

Interaction Info: Details of the Assay for Interaction Inhibition of wild type BRAF activity. Specific Action of the Ligand Inhibition Endogenous Drug? False

Publications: James et al., 2012, CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity., Mol. Cancer Ther.

Interaction Types: inhibitor

Interaction Info: Trial Name CHIR-265 Novel drug target Established target Specific Action of the Ligand Inhibition

Publications: Su et al., 2012, RAF265 inhibits the growth of advanced human melanoma tumors., Clin. Cancer Res. Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med

Interaction Types: inhibitor

Interaction Info: Indication/Tumor Type non-small cell lung carcinoma Response Type resistant Approval Status Preclinical - Pdx

Interaction Types: inhibitor

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? False

Interaction Types: inhibitor

Interaction Info: Drug family BRAF inhibitor Alteration BRAF:V600E Specific Action of the Ligand Inhibition

Interaction Types: inhibitor

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? False

Interaction Types: inhibitor

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? True

Interaction Types: inhibitor

Interaction Info: Details of the Assay for Interaction In a cell-free assay Specific Action of the Ligand Inhibition Endogenous Drug? False

Publications: Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med Karoulia et al., 2016, An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling., Cancer Cell

Interaction Types: inhibitor

Interaction Info: Notes combination therapy LGX818 + Cetuximab + BYL719 Indication/Tumor Type colorectal cancer

Interaction Types: inhibitor

Interaction Info: Drug family BCR-ABL inhibitor 2nd gen Alteration BRAF:Y472C Alteration BRAF:G466V

Interaction Types: inhibitor

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? False

Publications:

Interaction Types: inhibitor

Interaction Info: Trial Name XL281 Novel drug target Established target Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Publications:

Interaction Types: inhibitor

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Direct Interaction yes Notes Targets wildtype BRAF and BRAF with V600E mutation

Publications:

Interaction Types: inhibitor

Interaction Info: Reported Cancer Type Melanoma Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Direct Interaction yes

Publications:

Interaction Types: inhibitor

Interaction Info: Trial Name GSK2118436 Novel drug target Established target

Publications:

Interaction Types: inhibitor

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Direct Interaction yes

Publications:

Interaction Types: inhibitor

Interaction Info: Mechanism of Interaction RAF serine/threonine protein kinase inhibitor Direct Interaction yes Indication/Tumor Type Advanced Solid Tumor

Publications:

Interaction Types: inhibitor

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Direct Interaction yes

Publications:

Interaction Types: inhibitor

Interaction Info: Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor Direct Interaction yes

Publications:

Interaction Types: inhibitor

Interaction Info: combination therapy Dabrafenib;Trametinib Drug family BRAF inhibitor;MEK inhibitor Alteration BRAF:V600E

Interaction Types: inhibitor

Interaction Info: combination therapy Sorafenib + Temsirolimus Trial Name Nexavar Novel drug target Established target

Interaction Types: inhibitor

Interaction Info: Trial Name PLX4032, RG7204 Novel drug target Established target Drug family BRAF inhibitor

Interaction Types: inhibitor

Interaction Info: combination therapy Bevacizumab + Temsirolimus + Doxil Indication/Tumor Type ovarian carcinoma Response Type sensitive

Interaction Types: n/a

Interaction Info: Indication/Tumor Type melanoma Response Type no benefit Approval Status Preclinical

Publications: Peng et al., 2016, Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy., Cancer Discov

Interaction Types: n/a

Interaction Info: combination therapy Selumetinib + Paclitaxel Drug family MEK inhibitor Alteration BRAF__.

Interaction Types: n/a

Interaction Info: combination therapy Encorafenib + Binimetinib + Cetuximab combination therapy Binimetinib + BKM120 Indication/Tumor Type melanoma

Interaction Types: n/a

Interaction Info: Indication/Tumor Type colorectal cancer Response Type resistant Approval Status Preclinical

Interaction Types: n/a

Interaction Info: combination therapy Pimasertib + Sorafenib Indication/Tumor Type colorectal cancer Response Type sensitive

Publications: Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer

Interaction Types: n/a

Interaction Info: combination therapy Panitumumab;Dabrafenib;BYL719 Drug family EGFR mAb inhibitor;BRAF inhibitor;PI3K inhibitor Alteration BRAF:V600.

Interaction Types:

inhibitor

Interaction Info:

Details of the Assay for Interaction Inhibition of wild type BRAF kinase domain (aa416-766)

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

Tang et al., 2015, BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers., Mol. Cancer Ther.

Interaction Types:

inhibitor

Interaction Info:

Details of the Assay for Interaction Inhibition of wild type BRAF activity.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

James et al., 2012, CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity., Mol. Cancer Ther.

Interaction Types:

inhibitor

Interaction Info:

Trial Name CHIR-265

Novel drug target Established target

Specific Action of the Ligand Inhibition

Publications:

Su et al., 2012, RAF265 inhibits the growth of advanced human melanoma tumors., Clin. Cancer Res.

Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med

Interaction Types:

inhibitor

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Preclinical - Pdx

Interaction Types:

inhibitor

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types:

inhibitor

Interaction Info:

Drug family BRAF inhibitor

Alteration BRAF:V600E

Specific Action of the Ligand Inhibition

Interaction Types:

inhibitor

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types:

inhibitor

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Interaction Types:

inhibitor

Interaction Info:

Details of the Assay for Interaction In a cell-free assay

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

Whittaker et al., 2010, Gatekeeper mutations mediate resistance to BRAF-targeted therapies., Sci Transl Med

Karoulia et al., 2016, An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling., Cancer Cell

Interaction Types:

inhibitor

Interaction Info:

Notes

combination therapy LGX818 + Cetuximab + BYL719

Indication/Tumor Type colorectal cancer

Interaction Types:

inhibitor

Interaction Info:

Drug family BCR-ABL inhibitor 2nd gen

Alteration BRAF:Y472C

Alteration BRAF:G466V

Interaction Types:

inhibitor

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types:

inhibitor

Interaction Info:

Trial Name XL281

Novel drug target Established target

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Interaction Types:

inhibitor

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Notes Targets wildtype BRAF and BRAF with V600E mutation

Interaction Types:

inhibitor

Interaction Info:

Reported Cancer Type Melanoma

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Interaction Types:

inhibitor

Interaction Info:

Trial Name GSK2118436

Novel drug target Established target

Interaction Types:

inhibitor

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Interaction Types:

inhibitor

Interaction Info:

Mechanism of Interaction RAF serine/threonine protein kinase inhibitor

Direct Interaction yes

Indication/Tumor Type Advanced Solid Tumor

Interaction Types:

inhibitor

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Interaction Types:

inhibitor

Interaction Info:

Mechanism of Interaction Serine/threonine-protein kinase B-raf inhibitor

Direct Interaction yes

Interaction Types:

inhibitor

Interaction Info:

combination therapy Dabrafenib;Trametinib

Drug family BRAF inhibitor;MEK inhibitor

Alteration BRAF:V600E

Interaction Types:

inhibitor

Interaction Info:

combination therapy Sorafenib + Temsirolimus

Trial Name Nexavar

Novel drug target Established target

Interaction Types:

inhibitor

Interaction Info:

Trial Name PLX4032, RG7204

Novel drug target Established target

Drug family BRAF inhibitor

Interaction Types:

inhibitor

Interaction Info:

combination therapy Bevacizumab + Temsirolimus + Doxil

Indication/Tumor Type ovarian carcinoma

Response Type sensitive

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type no benefit

Approval Status Preclinical

Publications:

Peng et al., 2016, Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy., Cancer Discov

Interaction Types:

n/a

Interaction Info:

combination therapy Selumetinib + Paclitaxel

Drug family MEK inhibitor

Alteration BRAF__.

Interaction Types:

n/a

Interaction Info:

combination therapy Encorafenib + Binimetinib + Cetuximab

combination therapy Binimetinib + BKM120

Indication/Tumor Type melanoma

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type resistant

Approval Status Preclinical

Interaction Types:

n/a

Interaction Info:

combination therapy Pimasertib + Sorafenib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Publications:

Martinelli et al., 2013, Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells., Int. J. Cancer

Interaction Types:

n/a

Interaction Info:

combination therapy Panitumumab;Dabrafenib;BYL719

Drug family EGFR mAb inhibitor;BRAF inhibitor;PI3K inhibitor

Alteration BRAF:V600.

Interaction Types:

n/a

Interaction Info:

combination therapy GDC0879 + GDC-0941

Indication/Tumor Type melanoma

Response Type sensitive

Interaction Types:

n/a

Interaction Info:

combination therapy Vemurafenib + Gefitinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

Interaction Types:

n/a

Interaction Info:

combination therapy BEZ235 + Vemurafenib

Indication/Tumor Type melanoma

Response Type sensitive

Interaction Types:

n/a

Interaction Info:

combination therapy Cetuximab + Irinotecan

Indication/Tumor Type colorectal cancer

Response Type resistant

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Phase I

Interaction Types:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov

combination therapy	GDC0879 + GDC-0941
Indication/Tumor Type	melanoma
Response Type	sensitive

combination therapy	Vemurafenib + Gefitinib
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

combination therapy	BEZ235 + Vemurafenib
Indication/Tumor Type	melanoma
Response Type	sensitive

combination therapy	Cetuximab + Irinotecan
Indication/Tumor Type	colorectal cancer
Response Type	resistant

combination therapy	Everolimus + Selumetinib
Indication/Tumor Type	malignant glioma
Response Type	predicted – sensitive

combination therapy	Fluorouracil + Leucovorin + Trastuzumab
Indication/Tumor Type	rectum adenocarcinoma
Response Type	no benefit

combination therapy	PF3644022 + PF-477736
Indication/Tumor Type	lung adenocarcinoma
Response Type	predicted – sensitive

combination therapy	Lapatinib + Panobinostat
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

Indication/Tumor Type	skin melanoma
Response Type	sensitive
Approval Status	Preclinical - Cell line xenograft

combination therapy	PLX4720 + Tivozanib
Indication/Tumor Type	melanoma
Response Type	sensitive