DGIdb - KIT Gene Record

KIT 3815 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

3815
KIT PROTO-ONCOGENE RECEPTOR TYROSINE KINASE
KIT
C-Kit
CD117
PBT
SCFR
164920
6342
ENSG00000157404
OTTHUMG00000128713
Mast/stem cell growth factor receptor Kit
Proto-oncogene c-Kit
Tyrosine-protein kinase Kit
p145 c-kit
v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
Piebald trait protein
CD_antigen=CD117
BE0000453
P10721
KIT_HUMAN
MAST/STEM CELL GROWTH FACTOR RECEPTOR PRECURSOR (EC 2.7.1.112) (SCFR) (PROTO-ONCOGENE TYROSINE-PROTEIN KINASE KIT) (C-KIT) (CD117 ANTIGEN). [SOURCE:UNIPROT/SWISSPROT;ACC:P10721]
1805
29
NP_000213
NM_000222
KIT proto-oncogene, receptor tyrosine kinase
PA30128
T57700

Gene Info:

CancerCommons Reported Gene Name	KIT
CancerCommons Reported Gene Name	VEGF, PDGF
CancerCommons Reported Gene Name	Receptor tyrosine kinases KIT, CSF1R, and FLT3
Interpro Acc	IPR001245
Human Readable Name	DRUGGABLE GENOME
Interpro Type	Domain
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
Uniprot Status	Swiss-Prot
Human Readable Name	KINASE
Initial Gene Query	KIT
Counted Citations from 1950-2000	7271
Target Class	Receptors
Target Subclass	EC:2.7.10.1
Target Main Class	Receptors
Target Subclass	PDGFR
Target Subclass	KInase
Transmembrane Helix Count	1
GuideToPharmacology Gene Category Name	Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family
GuideToPharmacology Gene Category ID	322
Gene Biotype	PROTEIN_CODING

(29 More Sources)

Gene Categories: Category Details

KINASE
TYROSINE KINASE
DRUG RESISTANCE
EXTERNAL SIDE OF PLASMA MEMBRANE
DRUGGABLE GENOME
CLINICALLY ACTIONABLE
TRANSCRIPTION FACTOR

Publications:

Huynh et al., 2009, Sorafenib induces growth suppression in mouse models of gastrointestinal stromal tumor., Mol. Cancer Ther.
Quintás-Cardama et al., 2008, Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib., Nat Clin Pract Oncol
Allegra et al., 2014, A new KIT mutation (N505I) in acral melanoma confers constitutive signaling, favors tumorigenic properties, and is sensitive to imatinib., J. Invest. Dermatol.
Lierman et al., 2007, The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and overcome resistance to other small molecule inhibitors., Haematologica
Koch et al., 2006, Does the expression of c-kit (CD117) in neuroendocrine tumors represent a target for therapy?, Ann. N. Y. Acad. Sci.
Heinrich et al., 2012, Sorafenib inhibits many kinase mutations associated with drug-resistant gastrointestinal stromal tumors., Mol. Cancer Ther.
Schirosi et al., 2012, Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors., Ann. Oncol.
Guida et al., 2007, Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants., Clin. Cancer Res.
Liu et al., 2006, Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5., Cancer Res.
Gong L et al., 2017, PharmGKB summary: sorafenib pathways., Pharmacogenet Genomics
Woodman et al., 2009, Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates., Mol. Cancer Ther.
Handolias et al., 2010, Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT., Br. J. Cancer
Guo et al., 2007, Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor., Clin. Cancer Res.
Bisagni et al., 2009, Long lasting response to the multikinase inhibitor bay 43-9006 (Sorafenib) in a heavily pretreated metastatic thymic carcinoma., J Thorac Oncol
Falchook et al., 2015, Dual antiangiogenic inhibition: a phase I dose escalation and expansion trial targeting VEGF-A and VEGFR in patients with advanced solid tumors., Invest New Drugs
Cascone et al., 2007, Combined targeted therapies in non-small cell lung cancer: a winner strategy?, Curr Opin Oncol
Dişel et al., 2011, Promising efficacy of sorafenib in a relapsed thymic carcinoma with C-KIT exon 11 deletion mutation., Lung Cancer
Cannarile MA et al., 2017, Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy., J Immunother Cancer
Kim et al., 2014, Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal stromal tumor., Clin. Cancer Res.
Valent et al., 2015, Chronic mast cell leukemia (MCL) with KIT S476I: a rare entity defined by leukemic expansion of mature mast cells and absence of organ damage., Ann. Hematol.
Millward MJ et al., 2006, The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study., Br J Cancer
Gotlib et al., 2016, Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis., N. Engl. J. Med.
Caenepeel et al., 2010, Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors., J. Exp. Clin. Cancer Res.
Wasag et al., 2011, Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis., Exp. Hematol.
Johnson et al., 2013, Hidden mastocytosis in acute myeloid leukemia with t(8;21)(q22;q22)., Am. J. Clin. Pathol.
Marcucci G et al., 2020, Combination of dasatinib with chemotherapy in previously untreated core binding factor acute myeloid leukemia: CALGB 10801., Blood Adv
Gajiwala et al., 2009, KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients., Proc. Natl. Acad. Sci. U.S.A.
Gotlib et al., 2005, Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation., Blood
Cairoli et al., 2006, Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study., Blood
Gleixner et al., 2007, Synergistic growth-inhibitory effects of two tyrosine kinase inhibitors, dasatinib and PKC412, on neoplastic mast cells expressing the D816V-mutated oncogenic variant of KIT., Haematologica
Debiec-Rychter et al., 2005, Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants., Gastroenterology
Dizdar et al., 2008, Dasatinib may also inhibit c-Kit in triple negative breast cancer cell lines., Breast Cancer Res. Treat.
Mpakou et al., 2013, Dasatinib inhibits proliferation and induces apoptosis in the KASUMI-1 cell line bearing the t(8;21)(q22;q22) and the N822K c-kit mutation., Leuk. Res.
Carlino et al., 2014, Resistance to c-Kit inhibitors in melanoma: insights for future therapies., Oncoscience
Ustun et al., 2009, Chemotherapy and dasatinib induce long-term hematologic and molecular remission in systemic mastocytosis with acute myeloid leukemia with KIT D816V., Leuk. Res.
Emile et al., 2012, Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs., Med. Oncol.
Antonescu et al., 2007, L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition., Int. J. Cancer
Smith et al., 2012, Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia., Nature
Pan et al., 2007, EXEL-0862, a novel tyrosine kinase inhibitor, induces apoptosis in vitro and ex vivo in human mast cells expressing the KIT D816V mutation., Blood
Verstovsek et al., 2008, Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis., Clin. Cancer Res.
Smith et al., 2013, The role of kinase inhibitors in the treatment of patients with acute myeloid leukemia., Am Soc Clin Oncol Educ Book
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Hong et al., 2012, [Secondary mutation of c-kit/PDGFRα genotypes after imatinib mesylate therapy and its relationship with efficacy of sunitinib]., Zhonghua Bing Li Xue Za Zhi
Nakagomi et al., 2007, Juxtamembrane-type c-kit gene mutation found in aggressive systemic mastocytosis induces imatinib-resistant constitutive KIT activation., Lab. Invest.
Carvajal et al., 2011, KIT as a therapeutic target in metastatic melanoma., JAMA
Shah et al., 2006, Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis., Blood
Schittenhelm et al., 2006, Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies., Cancer Res.
Todd et al., 2013, Secondary c-Kit mutations confer acquired resistance to RTK inhibitors in c-Kit mutant melanoma cells., Pigment Cell Melanoma Res
Tornillo et al., 2006, An update on molecular genetics of gastrointestinal stromal tumours., J. Clin. Pathol.
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
Ben-Ami et al., 2016, Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy., Ann. Oncol.
Garner et al., 2014, Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients., Clin. Cancer Res.
Foster et al., 2008, Association of paediatric mastocytosis with a polymorphism resulting in an amino acid substitution (M541L) in the transmembrane domain of c-KIT., Br. J. Dermatol.
Rutkowski et al., 2007, Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs)., J. Cancer Res. Clin. Oncol.
Growney et al., 2005, Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412., Blood
Hirota et al., 1998, Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors., Science
McDonnell et al., 2011, V559A and N822I double KIT mutant melanoma with predictable response to imatinib?, Pigment Cell Melanoma Res
Handolias et al., 2010, Mutations in KIT occur at low frequency in melanomas arising from anatomical sites associated with chronic and intermittent sun exposure., Pigment Cell Melanoma Res
Spitaleri et al., 2015, Inactivity of imatinib in gastrointestinal stromal tumors (GISTs) harboring a KIT activation-loop domain mutation (exon 17 mutation pN822K)., Onco Targets Ther
Zook et al., 2017, Combination of Imatinib Mesylate and AKT Inhibitor Provides Synergistic Effects in Preclinical Study of Gastrointestinal Stromal Tumor., Clin. Cancer Res.
Li et al., 2015, FGFR-Mediated Reactivation of MAPK Signaling Attenuates Antitumor Effects of Imatinib in Gastrointestinal Stromal Tumors., Cancer Discov
Patrikidou et al., 2016, Long-term outcome of molecular subgroups of GIST patients treated with standard-dose imatinib in the BFR14 trial of the French Sarcoma Group., Eur. J. Cancer
Kitayama et al., 1995, Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factor-dependent hematopoietic cell lines., Blood
Tamborini et al., 2004, A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient., Gastroenterology
Cameron et al., 2011, Ten Years of Treatment with 400 mg Imatinib per Day in a Case of Advanced Gastrointestinal Stromal Tumor., Case Rep Oncol
Ströbel et al., 2004, Thymic carcinoma with overexpression of mutated KIT and the response to imatinib., N. Engl. J. Med.
Jachetti et al., 2017, Imatinib Spares cKit-Expressing Prostate Neuroendocrine Tumors, whereas Kills Seminal Vesicle Epithelial-Stromal Tumors by Targeting PDGFR-β., Mol. Cancer Ther.
Frost et al., 2002, Juxtamembrane mutant V560GKit is more sensitive to Imatinib (STI571) compared with wild-type c-kit whereas the kinase domain mutant D816VKit is resistant., Mol. Cancer Ther.
Iurlo et al., 2014, Identification of kit(M541L) somatic mutation in chronic eosinophilic leukemia, not otherwise specified and its implication in low-dose imatinib response., Oncotarget
Zeng S et al., 2017 Sep, Wnt/β-catenin Signaling Contributes to Tumor Malignancy and Is Targetable in Gastrointestinal Stromal Tumor., Mol Cancer Ther
Girard et al., 2009, Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas., Clin. Cancer Res.
Hirota et al., 2001, Gain-of-function mutation at the extracellular domain of KIT in gastrointestinal stromal tumours., J. Pathol.
Buti et al., 2011, Impressive response with imatinib in a heavily pretreated patient with metastatic c-KIT mutated thymic carcinoma., J. Clin. Oncol.
Prenen et al., 2006, Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate., Clin. Cancer Res.
Heinrich et al., 2017, Correlation of Long-term Results of Imatinib in Advanced Gastrointestinal Stromal Tumors With Next-Generation Sequencing Results: Analysis of Phase 3 SWOG Intergroup Trial S0033., JAMA Oncol
Hartmann et al., 2005, Novel germline mutation of KIT associated with familial gastrointestinal stromal tumors and mastocytosis., Gastroenterology
Guo et al., 2011, Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification., J. Clin. Oncol.
Hagemann et al., 2014, Stabilization of disease after targeted therapy in a thymic carcinoma with KIT mutation detected by clinical next-generation sequencing., J Thorac Oncol
Rossi et al., 2013, When a thymic carcinoma "becomes" a GIST., Lung Cancer
Beadling et al., 2008, KIT gene mutations and copy number in melanoma subtypes., Clin. Cancer Res.
Rapisuwon et al., 2014, Novel somatic KIT exon 8 mutation with dramatic response to imatinib in a patient with mucosal melanoma: a case report., Melanoma Res.
Heinrich et al., 2008, Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor., J. Clin. Oncol.
Conca et al., 2013, Are two better than one? A novel double-mutant KIT in GIST that responds to Imatinib., Mol Oncol
Serrano et al., 2015, KRAS and KIT Gatekeeper Mutations Confer Polyclonal Primary Imatinib Resistance in GI Stromal Tumors: Relevance of Concomitant Phosphatidylinositol 3-Kinase/AKT Dysregulation., J. Clin. Oncol.
Minor et al., 2012, Sunitinib therapy for melanoma patients with KIT mutations., Clin. Cancer Res.
Curtin et al., 2006, Somatic activation of KIT in distinct subtypes of melanoma., J. Clin. Oncol.
Debiec-Rychter et al., 2006, KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours., Eur. J. Cancer
Tefferi, 2009, Molecular drug targets in myeloproliferative neoplasms: mutant ABL1, JAK2, MPL, KIT, PDGFRA, PDGFRB and FGFR1., J. Cell. Mol. Med.
Antonescu et al., 2005, Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation., Clin. Cancer Res.
Hodi et al., 2008, Major response to imatinib mesylate in KIT-mutated melanoma., J. Clin. Oncol.
Terheyden et al., 2010, Response to imatinib mesylate depends on the presence of the V559A-mutated KIT oncogene., J. Invest. Dermatol.
Heinrich et al., 2008, Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group., J. Clin. Oncol.
Hodi et al., 2013, Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin., J. Clin. Oncol.
Carter et al., 2005, Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases., Proc. Natl. Acad. Sci. U.S.A.
Heinrich et al., 2003, Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor., J. Clin. Oncol.
Roberts et al., 2007, Resistance to c-KIT kinase inhibitors conferred by V654A mutation., Mol. Cancer Ther.
Tuveson DA et al., 2001, STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications., Oncogene
Dagher et al., 2002, Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors., Clin. Cancer Res.
Pectasides et al., Complete response after imatinib mesylate administration in a patient with chemoresistant stage IV seminoma., Anticancer Res.
Heinrich et al., 2006, Molecular correlates of imatinib resistance in gastrointestinal stromal tumors., J. Clin. Oncol.
Lee et al., 2006, Response to imatinib in KIT- and PDGFRA-wild type gastrointestinal stromal associated with neurofibromatosis type 1., Dig. Dis. Sci.
Goemans et al., 2005, Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia., Leukemia
Einhorn et al., 2006, Phase II study of imatinib mesylate in chemotherapy refractory germ cell tumors expressing KIT., Am. J. Clin. Oncol.
Tamborini et al., 2006, Functional analyses and molecular modeling of two c-Kit mutations responsible for imatinib secondary resistance in GIST patients., Oncogene
Dy et al., 2005, A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small-cell lung cancer: a CALGB and NCCTG study., Ann. Oncol.
Gebreyohannes et al., 2016, Cabozantinib Is Active against Human Gastrointestinal Stromal Tumor Xenografts Carrying Different KIT Mutations., Mol. Cancer Ther.
Posadas et al., 2007, A prospective analysis of imatinib-induced c-KIT modulation in ovarian cancer: a phase II clinical study with proteomic profiling., Cancer
Tutone et al., 2011, Study of the role of "gatekeeper" mutations V654A and T670I of c-kit kinase in the interaction with inhibitors by means mixed molecular dynamics/docking approach., Bioinformation
De Giorgi, 2007, KIT mutations and imatinib dose effects in patients with gastrointestinal stromal tumors., J. Clin. Oncol.
Joensuu et al., 2017, Effect of KIT and PDGFRA Mutations on Survival in Patients With Gastrointestinal Stromal Tumors Treated With Adjuvant Imatinib: An Exploratory Analysis of a Randomized Clinical Trial., JAMA Oncol
Kampa-Schittenhelm et al., 2013, Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms., Mol. Cancer
Joensuu, 2007, Second line therapies for the treatment of gastrointestinal stromal tumor., Curr Opin Oncol
Quek R et al., 2009, Gastrointestinal stromal tumor: a clinical overview., Hematol Oncol Clin North Am
Roskoski, 2007, Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor., Biochem. Biophys. Res. Commun.
Barattè et al., 2004, Quantitation of SU1 1248, an oral multi-target tyrosine kinase inhibitor, and its metabolite in monkey tissues by liquid chromatograph with tandem mass spectrometry following semi-automated liquid-liquid extraction., J Chromatogr A
Rutkowski et al., 2012, The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure - one institution study., BMC Cancer
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Abrams et al., 2003, SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer., Mol. Cancer Ther.
Reichardt et al., 2016, Correlation of KIT and PDGFRA mutational status with clinical benefit in patients with gastrointestinal stromal tumor treated with sunitinib in a worldwide treatment-use trial., BMC Cancer
Schueneman et al., 2003, SU11248 maintenance therapy prevents tumor regrowth after fractionated irradiation of murine tumor models., Cancer Res.
Sonpavde et al., 2007, Pazopanib: a novel multitargeted tyrosine kinase inhibitor., Curr Oncol Rep
Zhao et al., 2014, Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants., Cancer Sci.
Cohen et al., 2015, Pharmacological Inhibition of KIT Activates MET Signaling in Gastrointestinal Stromal Tumors., Cancer Res.
Wang et al., 2016, KIT Exon 11 Codons 557-558 Deletion Mutation Promotes Liver Metastasis Through the CXCL12/CXCR4 Axis in Gastrointestinal Stromal Tumors., Clin. Cancer Res.
Shen et al., 2017, Inactivation of Receptor Tyrosine Kinases Reverts Aberrant DNA Methylation in Acute Myeloid Leukemia., Clin. Cancer Res.
Delyon et al., 2017, STAT3 mediates Nilotinib response in KIT-altered Melanoma: a Phase II Multicenter Trial of the French Skin Cancer Network., J. Invest. Dermatol.
Cullinane et al., 2010, Preclinical evaluation of nilotinib efficacy in an imatinib-resistant KIT-driven tumor model., Mol. Cancer Ther.
Lee SJ et al., 2015, Phase II Trial of Nilotinib in Patients With Metastatic Malignant Melanoma Harboring KIT Gene Aberration: A Multicenter Trial of Korean Cancer Study Group (UN10-06)., Oncologist
Sawaki et al., 2011, Phase 2 study of nilotinib as third-line therapy for patients with gastrointestinal stromal tumor., Cancer
Cauchi et al., 2012, Evaluation of nilotinib in advanced GIST previously treated with imatinib and sunitinib., Cancer Chemother. Pharmacol.
Guo et al., 2017, Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial., Ann. Oncol.
Cho et al., 2012, Nilotinib in patients with metastatic melanoma harboring KIT gene aberration., Invest New Drugs
Carvajal et al., 2015, Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition., Clin. Cancer Res.
Jin et al., 2014, Ponatinib induces apoptosis in imatinib-resistant human mast cells by dephosphorylating mutant D816V KIT and silencing β-catenin signaling., Mol. Cancer Ther.
1976, [Pathomechanisms and progress in the therapy of hypertension. 4. Hannover Nephrological Symposium]., Med Monatsschr
Gozgit et al., 2011, Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies., Mol. Cancer Ther.
Huang et al., 2010, Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant., J. Med. Chem.
Lierman et al., 2012, Ponatinib is active against imatinib-resistant mutants of FIP1L1-PDGFRA and KIT, and against FGFR1-derived fusion kinases., Leukemia
Aghajanian, 1976, LSD and 2-bromo-LSD: comparison on effects on serotonergic neurones and on neurones in two serotonergic projection areas, the ventral lateral geniculate and amygdala., Neuropharmacology
Gleixner et al., 2013, Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V., Haematologica
Silen et al., 1975, Acid-base balance in amphibian gastric mucosa., Am. J. Physiol.
Matsui et al., 2008, E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition., Int. J. Cancer
Wu CP et al., 2019, Avapritinib: A Selective Inhibitor of KIT and PDGFRα that Reverses ABCB1 and ABCG2-Mediated Multidrug Resistance in Cancer Cell Lines., Mol Pharm
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)
Mahadevan et al., 2007, A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors., Oncogene
Liu P et al., 2020, The Use of Molecular Subtypes for Precision Therapy of Recurrent and Metastatic Gastrointestinal Stromal Tumor., Onco Targets Ther
Nemunaitis J et al., 2020, Intrigue: Phase III study of ripretinib versus sunitinib in advanced gastrointestinal stromal tumor after imatinib., Future Oncol
Rönnstrand L, 2004, Signal transduction via the stem cell factor receptor/c-Kit., Cell Mol Life Sci
Rolf MG et al., 2015, In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib., Pharmacol Res Perspect
Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov
Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

AVAPRITINIB KIT

Interaction Score: 2.24

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Phase I

PMIDs:
31117741

Sources:
OncoKB JAX-CKB TTD DrugBank GuideToPharmacology
QUIZARTINIB KIT

Interaction Score: 1.58

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Pathway activation

Clinical Status preclinical

Variant Effect gain-of-function

PMIDs:
23497317 21689725 24045550 19164557 15972446 16384925 18024392 18986703 22504184 16912224 23714533 25157968 17259998 23582185 16731599

Sources:
DoCM JAX-CKB GuideToPharmacology ChemblInteractions
ANCESTIM KIT

Interaction Score: 1.49

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

PMIDs:
15526160

Sources:
DrugBank
NILOTINIB KIT

Interaction Score: 1.26

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
28720666 28843487 20442311 25594040 26424760 21456006 17372901 25209843 22119758 28327988 22068222 25695690 19671763 17699867 23582185

Sources:
CancerCommons MyCancerGenomeClinicalTrial JAX-CKB CIViC DrugBank COSMIC CGI
IMATINIB KIT

Interaction Score: 1.1

Interaction Types & Directionality:

multitarget

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Approval Status Guideline

Indication/Tumor Type prostate neuroendocrine neoplasm

Approval Status Phase II

PMIDs:
18795925 17458563 15790786 9438854 21159146 21689725 20088873 26316776 24045550 27370604 18936790 24317392 25673643 26687836 7530509 15236194 19164557 22114577 15201427 15972446 16384925 18024392 27980106 12481435 15685537 25015329 28611108 19861435 11276010 25594040 21969494 16638875 28196207 18986703 21953054 16143141 21690468 24419427 23375402 18980976 22357254 17372901 22504184 25003536 18955458 23567324 24687822 22261812 16908931 16624552 19175693 16912224 25239608 15930355 18421059 19812602 18955451 23775962 23714533 19671763 25157968 20372153 16046538 17699867 22932406 14645423 17363509 11526490 17259998 12374669 21642685 18751412 16954519 16865565 16015387 16462496 16434489 16751810 16087693 23582185 27777285 17559139 22355224 17369583 28334365 16731599

Sources:
TEND OncoKB FDA PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank COSMIC TALC MyCancerGenome CGI
CHEMBL286939 KIT

Interaction Score: 0.75

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
17139284 17016423

Sources:
DrugBank
RIPRETINIB KIT

Interaction Score: 0.75

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type predicted – sensitive

Approval Status Phase I

PMIDs:
32273716 31755321

Sources:
JAX-CKB TTD DrugBank GuideToPharmacology
AMG-191 KIT

Interaction Score: 0.75

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
SUNITINIB KIT

Interaction Score: 0.64

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration KIT:449-514,550-592,627-664,664-714,788-828

Alteration KIT:788-828

Alteration KIT:Y553N

PMIDs:
19164557 17545799 19248971 19861435 25594040 21969494 17367763 16638875 21690468 23375402 22357254 18955458 22261812 25239608 14753710 22439647 11752352 18421059 21642685 12748309 23582185 26772734 12873999

Sources:
MyCancerGenomeClinicalTrial TEND OncoKB PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC DrugBank COSMIC TALC MyCancerGenome GuideToPharmacology CGI
AMUVATINIB KIT

Interaction Score: 0.64

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name MP-470

Novel drug target Established target

Mechanism of Interaction Stem cell growth factor receptor inhibitor

PMIDs:
17325667

Sources:
TdgClinicalTrial DrugBank TALC MyCancerGenome ChemblInteractions
MOTESANIB KIT

Interaction Score: 0.56

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Notes

PMIDs:
20633291

Sources:
JAX-CKB TdgClinicalTrial TALC MyCancerGenome ChemblInteractions
PEXIDARTINIB KIT

Interaction Score: 0.52

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

PMIDs:
28716061 24583793

Sources:
CancerCommons JAX-CKB TTD DrugBank MyCancerGenome GuideToPharmacology ChemblInteractions

OSI-930 KIT

Interaction Score: 0.43

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction The IC50 varied dependent on whether KIT was activated or unactivated, with the lower value measured for the activated enzyme.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
TTD DrugBank GuideToPharmacology ChemblInteractions

PONATINIB KIT

Interaction Score: 0.37

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor

Alteration KIT:788-828,829-860,550-592

Alteration KIT:A829P,V654A,T670I

PMIDs:
24552773 10517 21482694 20513156 22301675 25239608 10535 23539538 2015

Sources:
DTC JAX-CKB CIViC TTD DrugBank CGI
TELATINIB KIT

Interaction Score: 0.37

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Notes

PMIDs:
None found

Sources:
TALC MyCancerGenome ChemblInteractions
AKN-028 KIT

Interaction Score: 0.37

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
GuideToPharmacology
DASATINIB KIT

Interaction Score: 0.36

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Clinical Status preclinical

Clinical Status early trials

PMIDs:
21689725 24045550 32092139 19164557 15972446 16384925 18024392 15685537 17351742 23149070 25594040 18986703 21953054 17372901 22504184 16912224 18559612 23714533 19671763 25157968 17699867 22932406 17259998 21642685 16434489 16397263 23582185 16731599

Sources:
CancerCommons MyCancerGenomeClinicalTrial TEND DoCM JAX-CKB TdgClinicalTrial CIViC DrugBank TALC ChemblInteractions CGI
REGORAFENIB KIT

Interaction Score: 0.35

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Response Type decreased response

Approval Status Preclinical - Cell culture

Approval Status Phase II

PMIDs:
21170960 27371698 25239608

Sources:
MyCancerGenomeClinicalTrial OncoKB JAX-CKB CIViC TTD DrugBank TALC MyCancerGenome ChemblInteractions CGI
FAMITINIB KIT

Interaction Score: 0.32

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

PMIDs:
None found

Sources:
TTD GuideToPharmacology ChemblInteractions
MASITINIB KIT

Interaction Score: 0.32

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

PMIDs:
None found

Sources:
CancerCommons MyCancerGenomeClinicalTrial TdgClinicalTrial MyCancerGenome GuideToPharmacology ChemblInteractions
MIDOSTAURIN KIT

Interaction Score: 0.29

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type mast-cell leukemia

Response Type predicted – sensitive

Approval Status Preclinical - Patient cell culture

PMIDs:
25209843 16969355 27355533

Sources:
FDA PharmGKB JAX-CKB CIViC DrugBank MyCancerGenome ChemblInteractions
TANDUTINIB KIT

Interaction Score: 0.27

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
DTC MyCancerGenome GuideToPharmacology ChemblInteractions
SORAFENIB KIT

Interaction Score: 0.26

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Drug family Pan-TK inhibitor

Alteration KIT:550-592,627-664,788-828,829-860

Alteration KIT:D820E

PMIDs:
19139124 18936790 24317392 17229632 17102120 22665524 22357254 17545544 17178882 28362716 19671763 20372153 17699867 19461405 25363205 17272980 20970876

Sources:
TEND OncoKB PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank TALC MyCancerGenome GuideToPharmacology CGI
EDICOTINIB KIT

Interaction Score: 0.25

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
None found

Sources:
GuideToPharmacology
HENATINIB KIT

Interaction Score: 0.25

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
GuideToPharmacology
FLUMATINIB KIT

Interaction Score: 0.25

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
None found

Sources:
GuideToPharmacology
XL-820 KIT

Interaction Score: 0.25

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
TTD ChemblInteractions
CABOZANTINIB KIT

Interaction Score: 0.23

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Preclinical

PMIDs:
24205792 25836719 27777285

Sources:
JAX-CKB MyCancerGenome
VATALANIB KIT

Interaction Score: 0.23

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name vatalanib, PTK 787

Novel drug target Established target

Trial Name Vatalanib

PMIDs:
None found

Sources:
DTC TdgClinicalTrial TALC ChemblInteractions
AXITINIB KIT

Interaction Score: 0.21

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name axitinib, AG-013736

Novel drug target Established target

Reported Cancer Type Prostate

PMIDs:
None found

Sources:
CancerCommons TdgClinicalTrial TALC MyCancerGenome
CM-082 KIT

Interaction Score: 0.19

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
RIVOCERANIB KIT

Interaction Score: 0.19

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Assay used apatinib mesylate (YN968D1)

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology
CHEMBL1908396 KIT

Interaction Score: 0.19

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
None found

Sources:
GuideToPharmacology
SU-014813 KIT

Interaction Score: 0.19

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
GuideToPharmacology ChemblInteractions
CHEMBL406375 KIT

Interaction Score: 0.19

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
GuideToPharmacology
LENVATINIB KIT

Interaction Score: 0.16

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name E7080

Novel drug target Established target

PMIDs:
17943726

Sources:
TdgClinicalTrial DrugBank
ANLOTINIB KIT

Interaction Score: 0.15

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
IMATINIB MESYLATE KIT

Interaction Score: 0.15

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
TTD ChemblInteractions
CHEMBL1908395 KIT

Interaction Score: 0.15

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
None found

Sources:
GuideToPharmacology
PD-0325901 KIT

Interaction Score: 0.14

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Preclinical - Cell culture

PMIDs:
26936919

Sources:
JAX-CKB
PAZOPANIB KIT

Interaction Score: 0.1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
17288876

Sources:
MyCancerGenomeClinicalTrial DrugBank TALC MyCancerGenome GuideToPharmacology
SEMAXANIB KIT

Interaction Score: 0.1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
GuideToPharmacology ChemblInteractions
CRENOLANIB KIT

Interaction Score: 0.09

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
None found

Sources:
GuideToPharmacology
ROMIPLOSTIM KIT

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
TTD
MK-2206 KIT

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Imatinib + MK2206

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

PMIDs:
27370604

Sources:
JAX-CKB
SUNITINIB MALATE KIT

Interaction Score: 0.08

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Stem cell growth factor receptor inhibitor

PMIDs:
None found

Sources:
ChemblInteractions
BARASERTIB KIT

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
XL-999 KIT

Interaction Score: 0.07

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
PEMBROLIZUMAB KIT

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Pembrolizumab + Trametinib

Indication/Tumor Type melanoma

Response Type no benefit

PMIDs:
28514312

Sources:
JAX-CKB
PAZOPANIB HYDROCHLORIDE KIT

Interaction Score: 0.07

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Stem cell growth factor receptor inhibitor

PMIDs:
None found

Sources:
ChemblInteractions
INFIGRATINIB KIT

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy BGJ398 + Imatinib

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

PMIDs:
25673643

Sources:
JAX-CKB
LUCITANIB KIT

Interaction Score: 0.06

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
None found

Sources:
GuideToPharmacology
ENMD-2076 KIT

Interaction Score: 0.06

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Novel drug target Established target

PMIDs:
None found

Sources:
TdgClinicalTrial ChemblInteractions
ERDAFITINIB KIT

Interaction Score: 0.06

Interaction Types & Directionality:

substrate

Interaction Info:

PMIDs:
None found

Sources:
DrugBank
SITRAVATINIB KIT

Interaction Score: 0.06

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction In a biochemical enzyme activity assay.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology
FORETINIB KIT

Interaction Score: 0.05

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
SORAFENIB TOSYLATE KIT

Interaction Score: 0.05

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
CEDIRANIB KIT

Interaction Score: 0.05

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
TALC GuideToPharmacology ChemblInteractions
AST-487 KIT

Interaction Score: 0.04

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
DTC GuideToPharmacology
BEVACIZUMAB KIT

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Bevacizumab + Sorafenib

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

PMIDs:
25363205

Sources:
JAX-CKB
CYTARABINE KIT

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dasatinib + Cytarabine

Indication/Tumor Type acute myeloid leukemia

Response Type sensitive

PMIDs:
18986703

Sources:
JAX-CKB
TRAMETINIB KIT

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Clinical Study

Response Type no benefit

PMIDs:
28514312

Sources:
JAX-CKB
DOVITINIB KIT

Interaction Score: 0.03

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
ClearityFoundationClinicalTrial DTC GuideToPharmacology ChemblInteractions
LINIFANIB KIT

Interaction Score: 0.03

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
None found

Sources:
TdgClinicalTrial DrugBank GuideToPharmacology
CHEMBL578061 KIT

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CHEMBL541400 KIT

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CENISERTIB KIT

Interaction Score: 0.02

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

PMIDs:
None found

Sources:
DTC TALC MyCancerGenome
GW843682X KIT

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
SNS-314 KIT

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
RG-1530 KIT

Interaction Score: 0.02

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
None found

Sources:
DTC GuideToPharmacology
JNJ-7706621 KIT

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
ILORASERTIB KIT

Interaction Score: 0.01

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Measuring inhibition of kinase activity in a biochemical assay.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
DTC GuideToPharmacology
ENTRECTINIB KIT

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
SP-600125 KIT

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CYC-116 KIT

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
FOSTAMATINIB KIT

Interaction Score: 0.01

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
26516587

Sources:
DrugBank

Ensembl: ENSG00000157404
- Version: 101_38
Alternate Names:

KIT Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING

Publications:

RussLampel: ENSG00000157404

Version: 26-July-2011

Alternate Names:

MAST/STEM CELL GROWTH FACTOR RECEPTOR PRECURSOR (EC 2.7.1.112) (SCFR) (PROTO-ONCOGENE TYROSINE-PROTEIN KINASE KIT) (C-KIT) (CD117 ANTIGEN). [SOURCE:UNIPROT/SWISSPROT;ACC:P10721] Description

KIT Display Id

ENSG00000157404 Ensembl Gene Id

Gene Info:

Human Readable Name DRUGGABLE GENOME

Gene Categories:

DRUGGABLE GENOME

Publications:

BaderLabGenes: KIT
- Version: February-2014
Alternate Names:

3815 Entrez Gene ID

Gene Info:

Initial Gene Query KIT

Counted Citations from 1950-2000 7271

Gene Categories:

KINASE

Publications:
HopkinsGroom: P10721
- Version: 11-September-2012
Alternate Names:

MAST/STEM CELL GROWTH FACTOR RECEPTOR KIT Uniprot Protein Name

KIT_HUMAN Uniprot Id

P10721 Uniprot Accession

Gene Info:

Interpro Acc IPR001245

Human Readable Name DRUGGABLE GENOME

Interpro Type Domain

Gene Categories:

KINASE, DRUGGABLE GENOME

Publications:
TdgClinicalTrial: P10721
- Version: January-2014
Alternate Names:

KIT Gene Symbol

Gene Info:

Target Class Receptors

Target Subclass EC:2.7.10.1

Publications:
TEND: P10721
- Version: 01-August-2011
Alternate Names:

3815 Entrez Gene Id

P10721 Uniprot Accession

KIT_HUMAN Uniprot Id

Gene Info:

Target Main Class Receptors

Target Subclass PDGFR

Target Subclass KInase

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

3815 Entrez Gene ID

Gene Info:

CancerCommons Reported Gene Name KIT

CancerCommons Reported Gene Name VEGF, PDGF

CancerCommons Reported Gene Name Receptor tyrosine kinases KIT, CSF1R, and FLT3

Publications:
GuideToPharmacology: 3815
- Version: 29-September-2020
Alternate Names:

6342 HUGO Gene ID

6342 HUGO Gene Symbol

KIT proto-oncogene, receptor tyrosine kinase HUGO Gene Name

Gene Info:

GuideToPharmacology Gene Category Name Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family

GuideToPharmacology Gene Category ID 322

Publications:

JAX-CKB: KIT

Version: 27-September-2017

Alternate Names:

3815 CKB Entrez Id

KIT CKB Gene Synonym

C-Kit CKB Gene Synonym

Gene Info:

Publications:

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

Ben-Ami et al., 2016, Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy., Ann. Oncol.

Garner et al., 2014, Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients., Clin. Cancer Res.

PharmGKB: KIT

Version: 18-August-2020

Alternate Names:

PA30128 PharmGKB ID

Gene Info:

Publications:

Tuveson DA et al., 2001, STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications., Oncogene

Quek R et al., 2009, Gastrointestinal stromal tumor: a clinical overview., Hematol Oncol Clin North Am

Gong L et al., 2017, PharmGKB summary: sorafenib pathways., Pharmacogenet Genomics

CIViC: KIT

Version: 14-September-2020

Alternate Names:

3815 Entrez Gene ID

29 CIViC Gene ID

Gene Info:

Gene Categories:

DRUG RESISTANCE

Publications:

Woodman et al., 2009, Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates., Mol. Cancer Ther.

Guo et al., 2007, Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor., Clin. Cancer Res.

Bisagni et al., 2009, Long lasting response to the multikinase inhibitor bay 43-9006 (Sorafenib) in a heavily pretreated metastatic thymic carcinoma., J Thorac Oncol

DrugBank: BE0000453

Version: 5.1.7

Alternate Names:

KIT DrugBank Gene Name

P10721 UniProt Accession

3815 Entrez Gene Id

Gene Info:

Publications:

Lierman et al., 2007, The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and overcome resistance to other small molecule inhibitors., Haematologica

Koch et al., 2006, Does the expression of c-kit (CD117) in neuroendocrine tumors represent a target for therapy?, Ann. N. Y. Acad. Sci.

Guida et al., 2007, Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants., Clin. Cancer Res.

CGI: KIT

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

Quintás-Cardama et al., 2008, Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib., Nat Clin Pract Oncol

Handolias et al., 2010, Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT., Br. J. Cancer

Wasag et al., 2011, Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis., Exp. Hematol.

DoCM: KIT

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

Wasag et al., 2011, Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis., Exp. Hematol.

Johnson et al., 2013, Hidden mastocytosis in acute myeloid leukemia with t(8;21)(q22;q22)., Am. J. Clin. Pathol.

Gajiwala et al., 2009, KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients., Proc. Natl. Acad. Sci. U.S.A.

DTC: KIT

Version: 02-September-2020

Alternate Names:

Gene Info:

Publications:

Huang et al., 2010, Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant., J. Med. Chem.

ChemblInteractions: SCFR
- Version: chembl_23
Alternate Names:

SCFR GENE_SYMBOL

KIT GENE_SYMBOL

Mast/stem cell growth factor receptor Kit UNIPROT

Gene Info:

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

KIT Gene Symbol

Gene Info:

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

3815 Entrez Gene Id

KIT MyCancerGenome Gene Symbol

KIT MyCancerGenome Reported Gene Name

Gene Info:

Publications:
HingoraniCasas: ENSG00000157404
- Version: 31-May-2017
Alternate Names:

ENSG00000157404 Gene Symbol

KIT Ensembl Id

Gene Info:

Gene Categories:

DRUGGABLE GENOME

Publications:
OncoKB: KIT
- Version: 23-July-2020
Alternate Names:

3815 OncoKB Entrez Id

PBT OncoKB Gene Synonym

C-Kit OncoKB Gene Synonym

Gene Info:

Publications:
Pharos: KIT
- Version: 03-September-2020
Alternate Names:

Mast/stem cell growth factor receptor Kit Gene Name

P10721 UniProt ID

Gene Info:

Gene Categories:

KINASE, TRANSCRIPTION FACTOR

Publications:
GO: KIT
- Version: 05-September-2020
Alternate Names:

SCFR GO Gene Synonym

Gene Info:

Gene Categories:

TYROSINE KINASE, EXTERNAL SIDE OF PLASMA MEMBRANE

Publications:
Tempus: KIT
- Version: 11-November-2018
Alternate Names:

KIT Gene Symbol

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
dGene: KIT
- Version: 27-Jun-2013
Alternate Names:

3815 Gene ID

C-Kit dGene Synonym

CD117 dGene Synonym

Gene Info:

Gene Categories:

KINASE, TYROSINE KINASE

Publications:
TTD: Tyrosine-protein kinase Kit
- Version: 2020.06.01
Alternate Names:

KIT TTD Gene Abbreviation

T57700 TTD Target ID

Gene Info:

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

Gene Info:

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

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

Gene Info:

Publications:
FoundationOneGenes: KIT
- Version: 03-September-2020
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
CarisMolecularIntelligence: KIT
- Version: 04-September-2020
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
FDA: KIT
- Version: 04-September-2020
Alternate Names:

Gene Info:

Publications:
Oncomine: KIT
- Version: v3
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
COSMIC: KIT
- Version: 4-Sep-2020
Alternate Names:

Gene Info:

Gene Categories:

DRUG RESISTANCE

Publications:

Indication/Tumor Type	gastrointestinal stromal tumor
Response Type	sensitive
Approval Status	Phase I

Pathway	activation
Clinical Status	preclinical
Variant Effect	gain-of-function

Reported Cancer Type	Melanoma
Indication/Tumor Type	melanoma
Response Type	sensitive

Approval Status	Guideline
Indication/Tumor Type	prostate neuroendocrine neoplasm
Approval Status	Phase II

Alteration	KIT:449-514,550-592,627-664,664-714,788-828
Alteration	KIT:788-828
Alteration	KIT:Y553N

Trial Name	MP-470
Novel drug target	Established target
Mechanism of Interaction	Stem cell growth factor receptor inhibitor

Mechanism of Interaction	Stem cell growth factor receptor inhibitor
Direct Interaction	yes
Notes

Details of the Assay for Interaction	The IC50 varied dependent on whether KIT was activated or unactivated, with the lower value measured for the activated enzyme.
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

Drug family	BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor
Alteration	KIT:788-828,829-860,550-592
Alteration	KIT:A829P,V654A,T670I

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

Response Type	decreased response
Approval Status	Preclinical - Cell culture
Approval Status	Phase II

Indication/Tumor Type	mast-cell leukemia
Response Type	predicted – sensitive
Approval Status	Preclinical - Patient cell culture

Drug family	Pan-TK inhibitor
Alteration	KIT:550-592,627-664,788-828,829-860
Alteration	KIT:D820E

Trial Name	vatalanib, PTK 787
Novel drug target	Established target
Trial Name	Vatalanib

Trial Name	axitinib, AG-013736
Novel drug target	Established target
Reported Cancer Type	Prostate

Details of the Assay for Interaction	Assay used apatinib mesylate (YN968D1)
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

combination therapy	Imatinib + MK2206
Indication/Tumor Type	gastrointestinal stromal tumor
Response Type	sensitive

combination therapy	Pembrolizumab + Trametinib
Indication/Tumor Type	melanoma
Response Type	no benefit

combination therapy	BGJ398 + Imatinib
Indication/Tumor Type	gastrointestinal stromal tumor
Response Type	sensitive

Details of the Assay for Interaction	In a biochemical enzyme activity assay.
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

KIT Gene Record

KIT 3815 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type gastrointestinal stromal tumor Response Type sensitive Approval Status Phase I

PMIDs: 31117741

Sources: OncoKB JAX-CKB TTD DrugBank GuideToPharmacology

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Pathway activation Clinical Status preclinical Variant Effect gain-of-function

PMIDs: 23497317 21689725 24045550 19164557 15972446 16384925 18024392 18986703 22504184 16912224 23714533 25157968 17259998 23582185 16731599

Sources: DoCM JAX-CKB GuideToPharmacology ChemblInteractions

Interaction Types & Directionality: agonist (activating)

Interaction Info:

PMIDs: 15526160

Sources: DrugBank

Interaction Types & Directionality: antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info: Reported Cancer Type Melanoma Indication/Tumor Type melanoma Response Type sensitive

PMIDs: 28720666 28843487 20442311 25594040 26424760 21456006 17372901 25209843 22119758 28327988 22068222 25695690 19671763 17699867 23582185

Sources: CancerCommons MyCancerGenomeClinicalTrial JAX-CKB CIViC DrugBank COSMIC CGI

Interaction Types & Directionality: multitarget antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info: Approval Status Guideline Indication/Tumor Type prostate neuroendocrine neoplasm Approval Status Phase II

Sources: TEND OncoKB FDA PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank COSMIC TALC MyCancerGenome CGI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 17139284 17016423

Sources: DrugBank

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type gastrointestinal stromal tumor Response Type predicted – sensitive Approval Status Phase I

PMIDs: 32273716 31755321

Sources: JAX-CKB TTD DrugBank GuideToPharmacology

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: TTD

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Alteration KIT:449-514,550-592,627-664,664-714,788-828 Alteration KIT:788-828 Alteration KIT:Y553N

PMIDs: 19164557 17545799 19248971 19861435 25594040 21969494 17367763 16638875 21690468 23375402 22357254 18955458 22261812 25239608 14753710 22439647 11752352 18421059 21642685 12748309 23582185 26772734 12873999

Sources: MyCancerGenomeClinicalTrial TEND OncoKB PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC DrugBank COSMIC TALC MyCancerGenome GuideToPharmacology CGI

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name MP-470 Novel drug target Established target Mechanism of Interaction Stem cell growth factor receptor inhibitor

PMIDs: 17325667

Sources: TdgClinicalTrial DrugBank TALC MyCancerGenome ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Stem cell growth factor receptor inhibitor Direct Interaction yes Notes

PMIDs: 20633291

Sources: JAX-CKB TdgClinicalTrial TALC MyCancerGenome ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type gastrointestinal stromal tumor Response Type sensitive Approval Status Preclinical - Cell line xenograft

PMIDs: 28716061 24583793

Sources: CancerCommons JAX-CKB TTD DrugBank MyCancerGenome GuideToPharmacology ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction The IC50 varied dependent on whether KIT was activated or unactivated, with the lower value measured for the activated enzyme. Specific Action of the Ligand Inhibition Endogenous Drug? False

PMIDs: None found

Sources: TTD DrugBank GuideToPharmacology ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor Alteration KIT:788-828,829-860,550-592 Alteration KIT:A829P,V654A,T670I

PMIDs: 24552773 10517 21482694 20513156 22301675 25239608 10535 23539538 2015

Sources: DTC JAX-CKB CIViC TTD DrugBank CGI

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Stem cell growth factor receptor inhibitor Direct Interaction yes Notes

PMIDs: None found

Sources: TALC MyCancerGenome ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: None found

Sources: GuideToPharmacology

Interaction Types & Directionality: antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info: Reported Cancer Type Melanoma Clinical Status preclinical Clinical Status early trials

PMIDs: 21689725 24045550 32092139 19164557 15972446 16384925 18024392 15685537 17351742 23149070 25594040 18986703 21953054 17372901 22504184 16912224 18559612 23714533 19671763 25157968 17699867 22932406 17259998 21642685 16434489 16397263 23582185 16731599

Sources: CancerCommons MyCancerGenomeClinicalTrial TEND DoCM JAX-CKB TdgClinicalTrial CIViC DrugBank TALC ChemblInteractions CGI

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Response Type decreased response Approval Status Preclinical - Cell culture Approval Status Phase II

PMIDs: 21170960 27371698 25239608

Sources: MyCancerGenomeClinicalTrial OncoKB JAX-CKB CIViC TTD DrugBank TALC MyCancerGenome ChemblInteractions CGI

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: None found

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Phase I

PMIDs:
31117741

Sources:
OncoKB JAX-CKB TTD DrugBank GuideToPharmacology

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Pathway activation

Clinical Status preclinical

Variant Effect gain-of-function

PMIDs:
23497317 21689725 24045550 19164557 15972446 16384925 18024392 18986703 22504184 16912224 23714533 25157968 17259998 23582185 16731599

Sources:
DoCM JAX-CKB GuideToPharmacology ChemblInteractions

Interaction Types & Directionality:

agonist (activating)

PMIDs:
15526160

Sources:
DrugBank

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
28720666 28843487 20442311 25594040 26424760 21456006 17372901 25209843 22119758 28327988 22068222 25695690 19671763 17699867 23582185

Sources:
CancerCommons MyCancerGenomeClinicalTrial JAX-CKB CIViC DrugBank COSMIC CGI

Interaction Types & Directionality:

multitarget

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Approval Status Guideline

Indication/Tumor Type prostate neuroendocrine neoplasm

Approval Status Phase II

Sources:
TEND OncoKB FDA PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank COSMIC TALC MyCancerGenome CGI

Interaction Types & Directionality:

n/a

PMIDs:
17139284 17016423

Sources:
DrugBank

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type predicted – sensitive

Approval Status Phase I

PMIDs:
32273716 31755321

Sources:
JAX-CKB TTD DrugBank GuideToPharmacology

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
TTD

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration KIT:449-514,550-592,627-664,664-714,788-828

Alteration KIT:788-828

Alteration KIT:Y553N

PMIDs:
19164557 17545799 19248971 19861435 25594040 21969494 17367763 16638875 21690468 23375402 22357254 18955458 22261812 25239608 14753710 22439647 11752352 18421059 21642685 12748309 23582185 26772734 12873999

Sources:
MyCancerGenomeClinicalTrial TEND OncoKB PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC DrugBank COSMIC TALC MyCancerGenome GuideToPharmacology CGI

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name MP-470

Novel drug target Established target

Mechanism of Interaction Stem cell growth factor receptor inhibitor

PMIDs:
17325667

Sources:
TdgClinicalTrial DrugBank TALC MyCancerGenome ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Notes

PMIDs:
20633291

Sources:
JAX-CKB TdgClinicalTrial TALC MyCancerGenome ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

PMIDs:
28716061 24583793

Sources:
CancerCommons JAX-CKB TTD DrugBank MyCancerGenome GuideToPharmacology ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction The IC50 varied dependent on whether KIT was activated or unactivated, with the lower value measured for the activated enzyme.

Specific Action of the Ligand Inhibition

Endogenous Drug? False

PMIDs:
None found

Sources:
TTD DrugBank GuideToPharmacology ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Drug family BCR-ABL inhibitor 3rd gen&Pan-TK inhibitor

Alteration KIT:788-828,829-860,550-592

Alteration KIT:A829P,V654A,T670I

PMIDs:
24552773 10517 21482694 20513156 22301675 25239608 10535 23539538 2015

Sources:
DTC JAX-CKB CIViC TTD DrugBank CGI

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Notes

PMIDs:
None found

Sources:
TALC MyCancerGenome ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
GuideToPharmacology

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Clinical Status preclinical

Clinical Status early trials

PMIDs:
21689725 24045550 32092139 19164557 15972446 16384925 18024392 15685537 17351742 23149070 25594040 18986703 21953054 17372901 22504184 16912224 18559612 23714533 19671763 25157968 17699867 22932406 17259998 21642685 16434489 16397263 23582185 16731599

Sources:
CancerCommons MyCancerGenomeClinicalTrial TEND DoCM JAX-CKB TdgClinicalTrial CIViC DrugBank TALC ChemblInteractions CGI

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Response Type decreased response

Approval Status Preclinical - Cell culture

Approval Status Phase II

PMIDs:
21170960 27371698 25239608

Sources:
MyCancerGenomeClinicalTrial OncoKB JAX-CKB CIViC TTD DrugBank TALC MyCancerGenome ChemblInteractions CGI

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

PMIDs:
None found

Sources:
TTD GuideToPharmacology ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

PMIDs:
None found

Sources:
CancerCommons MyCancerGenomeClinicalTrial TdgClinicalTrial MyCancerGenome GuideToPharmacology ChemblInteractions

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type mast-cell leukemia

Response Type predicted – sensitive

Approval Status Preclinical - Patient cell culture

PMIDs:
25209843 16969355 27355533

Sources:
FDA PharmGKB JAX-CKB CIViC DrugBank MyCancerGenome ChemblInteractions

combination therapy	Bevacizumab + Sorafenib
Indication/Tumor Type	gastrointestinal stromal tumor
Response Type	sensitive

combination therapy	Dasatinib + Cytarabine
Indication/Tumor Type	acute myeloid leukemia
Response Type	sensitive

Evidence Type	Actionable
Approval Status	Clinical Study
Response Type	no benefit

Details of the Assay for Interaction	Measuring inhibition of kinase activity in a biochemical assay.
Specific Action of the Ligand	Inhibition
Endogenous Drug?	False

MAST/STEM CELL GROWTH FACTOR RECEPTOR PRECURSOR (EC 2.7.1.112) (SCFR) (PROTO-ONCOGENE TYROSINE-PROTEIN KINASE KIT) (C-KIT) (CD117 ANTIGEN). [SOURCE:UNIPROT/SWISSPROT;ACC:P10721]	Description
KIT	Display Id
ENSG00000157404	Ensembl Gene Id

MAST/STEM CELL GROWTH FACTOR RECEPTOR KIT	Uniprot Protein Name
KIT_HUMAN	Uniprot Id
P10721	Uniprot Accession

3815	Entrez Gene Id
P10721	Uniprot Accession
KIT_HUMAN	Uniprot Id

6342	HUGO Gene ID
6342	HUGO Gene Symbol
KIT proto-oncogene, receptor tyrosine kinase	HUGO Gene Name

KIT	DrugBank Gene Name
P10721	UniProt Accession
3815	Entrez Gene Id

SCFR	GENE_SYMBOL
KIT	GENE_SYMBOL
Mast/stem cell growth factor receptor Kit	UNIPROT