DGIdb - KIT Gene Record

KIT 3815 Druggable GenomeClinically Actionable

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]
TTDS00270
CD117 ANTIGEN
MAST/STEM CELL GROWTH FACTOR RECEPTOR
PROTO-ONCOGENE TYROSINE-PROTEIN KINASE KIT
1805
29
NP_000213
NM_000222
KIT proto-oncogene, receptor tyrosine kinase
PA30128
T57700
MASTC

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
Source Reported Gene Name	KIT
Initial Gene Query	KIT
Counted Citations from 1950-2000	7271
Target Class	Receptors
Target Subclass	EC:2.7.10.1
Human Readable Name	TYROSINE KINASE
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
GuideToPharmacology Gene Type	catalytic_receptor
Gene Biotype	PROTEIN_CODING

(29 More Sources)

Gene Categories: Category Details

CELL SURFACE
KINASE
SERINE THREONINE KINASE
TYROSINE KINASE
PHOSPHOLIPASE
EXTERNAL SIDE OF PLASMA MEMBRANE
DRUGGABLE GENOME
LIPID KINASE
CLINICALLY ACTIONABLE
TRANSCRIPTION FACTOR

Publications:

Handolias et al., 2010, Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT., Br. J. Cancer
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
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
Guo et al., 2007, Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor., Clin. Cancer Res.
Schirosi et al., 2012, Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors., Ann. Oncol.
Woodman et al., 2009, Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates., Mol. Cancer Ther.
Cascone et al., 2007, Combined targeted therapies in non-small cell lung cancer: a winner strategy?, Curr Opin Oncol
Koch et al., 2006, Does the expression of c-kit (CD117) in neuroendocrine tumors represent a target for therapy?, Ann. N. Y. Acad. Sci.
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.
Guida et al., 2007, Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants., Clin. Cancer Res.
Lierman et al., 2007, The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and overcome resistance to other small molecule inhibitors., Haematologica
Heinrich et al., 2012, Sorafenib inhibits many kinase mutations associated with drug-resistant gastrointestinal stromal tumors., Mol. Cancer Ther.
Dişel et al., 2011, Promising efficacy of sorafenib in a relapsed thymic carcinoma with C-KIT exon 11 deletion mutation., Lung Cancer
Huynh et al., 2009, Sorafenib induces growth suppression in mouse models of gastrointestinal stromal tumor., Mol. Cancer Ther.
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
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.
Gong L et al., 2017, PharmGKB summary: sorafenib pathways., Pharmacogenet Genomics
Weisberg E et al., 2019, Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignancies., Br J Haematol
Kim et al., 2014, Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal stromal tumor., Clin. Cancer Res.
Cannarile MA et al., 2017, Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy., J Immunother Cancer
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.
Gotlib et al., 2016, Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis., N. Engl. J. Med.
Smith BD et al., 2019, Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants., Cancer Cell
Apsel Winger B et al., 2019, ATP-Competitive Inhibitors Midostaurin and Avapritinib Have Distinct Resistance Profiles in Exon 17-Mutant KIT., Cancer Res
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
Caenepeel et al., 2010, Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors., J. Exp. Clin. Cancer Res.
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
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.
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
Carvajal et al., 2011, KIT as a therapeutic target in metastatic melanoma., JAMA
Verstovsek et al., 2008, Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis., Clin. Cancer Res.
Tornillo et al., 2006, An update on molecular genetics of gastrointestinal stromal tumours., J. Clin. Pathol.
Cairoli et al., 2006, Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study., Blood
Nakagomi et al., 2007, Juxtamembrane-type c-kit gene mutation found in aggressive systemic mastocytosis induces imatinib-resistant constitutive KIT activation., Lab. Invest.
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
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
Todd et al., 2013, Secondary c-Kit mutations confer acquired resistance to RTK inhibitors in c-Kit mutant melanoma cells., Pigment Cell Melanoma Res
Gotlib et al., 2005, Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation., Blood
Smith et al., 2013, The role of kinase inhibitors in the treatment of patients with acute myeloid leukemia., Am Soc Clin Oncol Educ Book
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.
Wasag et al., 2011, Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis., Exp. Hematol.
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.
Smith et al., 2012, Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia., Nature
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Johnson et al., 2013, Hidden mastocytosis in acute myeloid leukemia with t(8;21)(q22;q22)., Am. J. Clin. Pathol.
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.
Carlino et al., 2014, Resistance to c-Kit inhibitors in melanoma: insights for future therapies., Oncoscience
Dizdar et al., 2008, Dasatinib may also inhibit c-Kit in triple negative breast cancer cell lines., Breast Cancer Res. Treat.
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
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
Zhan Y et al., 2017, MNK1/2 inhibition limits oncogenicity and metastasis of KIT-mutant melanoma., J Clin Invest
Tarlock K et al., 2019, Functional Properties of <i>KIT</i> Mutations Are Associated with Differential Clinical Outcomes and Response to Targeted Therapeutics in CBF Acute Myeloid Leukemia., Clin Cancer Res
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.
Na YS et al., 2017, Establishment and characterization of patient-derived xenograft models of gastrointestinal stromal tumor resistant to standard tyrosine kinase inhibitors., Oncotarget
Banks E et al., 2020, Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors., Sci Transl Med
Tuveson DA et al., 2001, STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications., Oncogene
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
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.
Dagher et al., 2002, Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors., Clin. Cancer Res.
Einhorn et al., 2006, Phase II study of imatinib mesylate in chemotherapy refractory germ cell tumors expressing KIT., Am. J. Clin. Oncol.
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.
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
Tamborini et al., 2006, Functional analyses and molecular modeling of two c-Kit mutations responsible for imatinib secondary resistance in GIST patients., Oncogene
Pectasides et al., Complete response after imatinib mesylate administration in a patient with chemoresistant stage IV seminoma., Anticancer Res.
Ströbel et al., 2004, Thymic carcinoma with overexpression of mutated KIT and the response to imatinib., N. Engl. J. Med.
Growney et al., 2005, Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412., Blood
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.
Terheyden et al., 2010, Response to imatinib mesylate depends on the presence of the V559A-mutated KIT oncogene., J. Invest. Dermatol.
Buti et al., 2011, Impressive response with imatinib in a heavily pretreated patient with metastatic c-KIT mutated thymic carcinoma., J. Clin. Oncol.
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
Conca et al., 2013, Are two better than one? A novel double-mutant KIT in GIST that responds to Imatinib., Mol Oncol
Tamborini et al., 2004, A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient., Gastroenterology
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
Heinrich et al., 2006, Molecular correlates of imatinib resistance in gastrointestinal stromal tumors., J. Clin. Oncol.
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
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
Zeng S et al., 2017 Sep, Wnt/β-catenin Signaling Contributes to Tumor Malignancy and Is Targetable in Gastrointestinal Stromal Tumor., Mol Cancer Ther
Goemans et al., 2005, Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia., Leukemia
Zook et al., 2017, Combination of Imatinib Mesylate and AKT Inhibitor Provides Synergistic Effects in Preclinical Study of Gastrointestinal Stromal Tumor., Clin. Cancer Res.
Gebreyohannes et al., 2016, Cabozantinib Is Active against Human Gastrointestinal Stromal Tumor Xenografts Carrying Different KIT Mutations., Mol. Cancer Ther.
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.
Girard et al., 2009, Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas., Clin. Cancer Res.
Li et al., 2015, FGFR-Mediated Reactivation of MAPK Signaling Attenuates Antitumor Effects of Imatinib in Gastrointestinal Stromal Tumors., Cancer Discov
Debiec-Rychter et al., 2006, KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours., Eur. J. Cancer
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.
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.
Minor et al., 2012, Sunitinib therapy for melanoma patients with KIT mutations., Clin. Cancer Res.
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.
Hodi et al., 2008, Major response to imatinib mesylate in KIT-mutated melanoma., J. Clin. Oncol.
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.
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.
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
Lee et al., 2006, Response to imatinib in KIT- and PDGFRA-wild type gastrointestinal stromal associated with neurofibromatosis type 1., Dig. Dis. Sci.
De Giorgi, 2007, KIT mutations and imatinib dose effects in patients with gastrointestinal stromal tumors., J. Clin. Oncol.
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
Heinrich et al., 2003, Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor., 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.
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
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.
Roberts et al., 2007, Resistance to c-KIT kinase inhibitors conferred by V654A mutation., Mol. Cancer Ther.
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
Prenen et al., 2006, Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate., Clin. Cancer Res.
Antonescu et al., 2005, Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation., Clin. Cancer Res.
Hirota et al., 1998, Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors., Science
Curtin et al., 2006, Somatic activation of KIT in distinct subtypes of melanoma., J. Clin. Oncol.
Hirota et al., 2001, Gain-of-function mutation at the extracellular domain of KIT in gastrointestinal stromal tumours., J. Pathol.
Carter et al., 2005, Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases., Proc. Natl. Acad. Sci. U.S.A.
Beadling et al., 2008, KIT gene mutations and copy number in melanoma subtypes., Clin. Cancer Res.
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
Tefferi, 2009, Molecular drug targets in myeloproliferative neoplasms: mutant ABL1, JAK2, MPL, KIT, PDGFRA, PDGFRB and FGFR1., J. Cell. Mol. Med.
Rossi et al., 2013, When a thymic carcinoma "becomes" a GIST., Lung Cancer
Nishida T et al., 2008, Secondary mutations in the kinase domain of the KIT gene are predominant in imatinib-resistant gastrointestinal stromal tumor., Cancer Sci
Mussi C et al., 2008, Therapeutic consequences from molecular biology for gastrointestinal stromal tumor patients affected by neurofibromatosis type 1., Clin Cancer Res
Abdou Y et al., 2019, Combination of pembrolizumab and imatinib in a patient with double KIT mutant melanoma: A case report., Medicine (Baltimore)
Orlova KV et al., 2019, Lack of Response to Imatinib in Melanoma Carrying Rare <i>KIT</i> Mutation p.T632I., Case Rep Oncol
Zhao et al., 2014, Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants., Cancer Sci.
Lim KH et al., 2008, Molecular analysis of secondary kinase mutations in imatinib-resistant gastrointestinal stromal tumors., Med Oncol
Casali PG et al., 2018, Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up., Ann Oncol
Chow LW et al., 2008, Evaluation of neoadjuvant inhibition of aromatase activity and signal transduction in breast cancer., Cancer Lett
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
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
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
Joensuu, 2007, Second line therapies for the treatment of gastrointestinal stromal tumor., Curr Opin Oncol
Roskoski, 2007, Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor., Biochem. Biophys. Res. Commun.
Schueneman et al., 2003, SU11248 maintenance therapy prevents tumor regrowth after fractionated irradiation of murine tumor models., Cancer Res.
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
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.
Quek R et al., 2009, Gastrointestinal stromal tumor: a clinical overview., Hematol Oncol Clin North Am
Liu F et al., 2019, Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors., Ther Adv Med Oncol
Xu J et al., 2019, Inhibition of N822K T>A mutation-induced constitutive c-KIT activation in AML cells triggers apoptotic and autophagic pathways leading to death., Int J Med Sci
Sonpavde et al., 2007, Pazopanib: a novel multitargeted tyrosine kinase inhibitor., Curr Oncol Rep
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.
Cullinane et al., 2010, Preclinical evaluation of nilotinib efficacy in an imatinib-resistant KIT-driven tumor model., Mol. Cancer Ther.
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.
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.
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.
Carvajal et al., 2015, Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition., Clin. Cancer Res.
Cho et al., 2012, Nilotinib in patients with metastatic melanoma harboring KIT gene aberration., Invest New Drugs
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
1976, [Pathomechanisms and progress in the therapy of hypertension. 4. Hannover Nephrological Symposium]., Med Monatsschr
Silen et al., 1975, Acid-base balance in amphibian gastric mucosa., Am. J. Physiol.
Lierman et al., 2012, Ponatinib is active against imatinib-resistant mutants of FIP1L1-PDGFRA and KIT, and against FGFR1-derived fusion kinases., Leukemia
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.
Gozgit et al., 2011, Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies., Mol. Cancer Ther.
Gleixner et al., 2013, Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V., Haematologica
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.
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
Gebreyohannes YK et al., 2019, Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal Tumors., Clin Cancer Res
Evans EK et al., 2017, A precision therapy against cancers driven by <i>KIT/PDGFRA</i> mutations., Sci Transl Med
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
Janku F et al., 2020, Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal Stromal Tumor: A Phase I Study of Ripretinib., J Clin Oncol
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
Liu X et al., 2019, Preclinical development of HQP1351, a multikinase inhibitor targeting a broad spectrum of mutant KIT kinases, for the treatment of imatinib-resistant gastrointestinal stromal tumors., Cell Biosci
McCoach CE et al., 2018, Resistance Mechanisms to Targeted Therapies in <i>ROS1</i><sup>+</sup> and <i>ALK</i><sup>+</sup> Non-small Cell Lung Cancer., Clin Cancer Res
Katayama et al., 2012, Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers., Sci Transl Med
Hall TG et al., 2016, Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation., PLoS One
Rolf MG et al., 2015, In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib., Pharmacol Res Perspect
Rönnstrand L, 2004, Signal transduction via the stem cell factor receptor/c-Kit., Cell Mol Life Sci

SORAFENIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Drug family Pan-TK inhibitor

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

Alteration KIT:D820E

Publications:

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

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

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

PEXIDARTINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Kim et al., 2014, Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal stromal tumor., Clin. Cancer Res.

Cannarile MA et al., 2017, Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy., J Immunother Cancer

MIDOSTAURIN KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Indication/Tumor Type mast-cell leukemia

Response Type predicted – sensitive

Approval Status Preclinical - Patient cell culture

Publications:

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.

Gotlib et al., 2016, Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis., N. Engl. J. Med.

Smith BD et al., 2019, Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants., Cancer Cell

MOTESANIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Notes

Publications:

Caenepeel et al., 2010, Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors., J. Exp. Clin. Cancer Res.

DASATINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Clinical Status preclinical

Clinical Status early trials

Publications:

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

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.

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

REGORAFENIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Response Type decreased response

Approval Status Preclinical - Cell culture

Approval Status Phase II

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.

SUNITINIB KIT

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

Publications:

Minor et al., 2012, Sunitinib therapy for melanoma patients with KIT mutations., Clin. Cancer Res.

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.

Carvajal et al., 2011, KIT as a therapeutic target in metastatic melanoma., JAMA

AXITINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name axitinib, AG-013736

Novel drug target Established target

Reported Cancer Type Prostate

Publications:

Liu F et al., 2019, Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors., Ther Adv Med Oncol
PAZOPANIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

Sonpavde et al., 2007, Pazopanib: a novel multitargeted tyrosine kinase inhibitor., Curr Oncol Rep

CABOZANTINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Preclinical

Publications:

Zhao et al., 2014, Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants., Cancer Sci.

Gebreyohannes et al., 2016, Cabozantinib Is Active against Human Gastrointestinal Stromal Tumor Xenografts Carrying Different KIT Mutations., Mol. Cancer Ther.

Cohen et al., 2015, Pharmacological Inhibition of KIT Activates MET Signaling in Gastrointestinal Stromal Tumors., Cancer Res.

FLUMATINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:

Zhao et al., 2014, Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants., Cancer Sci.

NILOTINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Indication/Tumor Type melanoma

Response Type sensitive

Publications:

Cullinane et al., 2010, Preclinical evaluation of nilotinib efficacy in an imatinib-resistant KIT-driven tumor model., Mol. Cancer Ther.

Guo et al., 2007, Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation 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.

PONATINIB KIT

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

Publications:

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.

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

1976, [Pathomechanisms and progress in the therapy of hypertension. 4. Hannover Nephrological Symposium]., Med Monatsschr

AVAPRITINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Phase I

Publications:

Gebreyohannes YK et al., 2019, Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal Tumors., Clin Cancer Res

Banks E et al., 2020, Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors., Sci Transl Med

Smith BD et al., 2019, Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants., Cancer Cell

AMUVATINIB KIT

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

Publications:

Mahadevan et al., 2007, A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors., Oncogene

CRENOLANIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:

Tarlock K et al., 2019, Functional Properties of KIT Mutations Are Associated with Differential Clinical Outcomes and Response to Targeted Therapeutics in CBF Acute Myeloid Leukemia., Clin Cancer Res

Weisberg E et al., 2019, Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignancies., Br J Haematol

RIPRETINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type predicted – sensitive

Approval Status Phase I

Publications:

Banks E et al., 2020, Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors., Sci Transl Med

Smith BD et al., 2019, Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants., Cancer Cell

Janku F et al., 2020, Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal Stromal Tumor: A Phase I Study of Ripretinib., J Clin Oncol

OSI-930 KIT

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

Publications:

XL-820 KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Publications:
TANDUTINIB KIT

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

Publications:
SITRAVATINIB KIT

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

Publications:
chembl:CHEMBL406375 KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Publications:
SU-014813 KIT

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

Publications:
ENMD-2076 KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Novel drug target Established target

Publications:
AKN-028 KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Publications:
SUNITINIB MALATE KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Publications:
SEMAXANIB KIT

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

Publications:
PAZOPANIB HYDROCHLORIDE KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Publications:
CEDIRANIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:
VATALANIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name vatalanib, PTK 787

Novel drug target Established target

Trial Name Vatalanib

Publications:
AST-487 KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Publications:
MASITINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Publications:
ILORASERTIB KIT

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

Publications:
LINIFANIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:
chembl:CHEMBL1908396 KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:
TELATINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Notes

Publications:
chembl:CHEMBL1908395 KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:
DOVITINIB KIT

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

Publications:
RIVOCERANIB KIT

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

Publications:
FAMITINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

Publications:
HENATINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Publications:
FORETINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Publications:
IMATINIB MESYLATE KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Publications:
ANLOTINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Publications:
XL-999 KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Publications:
LUCITANIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:
CM-082 KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Publications:
EDICOTINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:
SORAFENIB TOSYLATE KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Publications:
RG-1530 KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:

IMATINIB KIT

Interaction Types & Directionality:

multitarget

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Approval Status Guideline

Indication/Tumor Type prostate neuroendocrine neoplasm

Approval Status Phase II

Publications:

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

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

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.

QUIZARTINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Pathway activation

Clinical Status preclinical

Variant Effect gain-of-function

Publications:

Tornillo et al., 2006, An update on molecular genetics of gastrointestinal stromal tumours., J. Clin. Pathol.

Cairoli et al., 2006, Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study., Blood

Nakagomi et al., 2007, Juxtamembrane-type c-kit gene mutation found in aggressive systemic mastocytosis induces imatinib-resistant constitutive KIT activation., Lab. Invest.

LENVATINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name E7080

Novel drug target Established target

Publications:

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

FOSTAMATINIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Publications:

Rolf MG et al., 2015, In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib., Pharmacol Res Perspect
ANCESTIM KIT

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Publications:

Rönnstrand L, 2004, Signal transduction via the stem cell factor receptor/c-Kit., Cell Mol Life Sci
CENISERTIB KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Publications:
ERDAFITINIB KIT

Interaction Types & Directionality:

substrate

Interaction Info:

Publications:
PD-0325901 KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

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.
MK-2206 KIT

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Imatinib + MK2206

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Publications:

Zook et al., 2017, Combination of Imatinib Mesylate and AKT Inhibitor Provides Synergistic Effects in Preclinical Study of Gastrointestinal Stromal Tumor., Clin. Cancer Res.
BEVACIZUMAB KIT

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Bevacizumab + Sorafenib

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Publications:

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
TRAMETINIB KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Clinical Study

Response Type no benefit

Publications:

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)

PEMBROLIZUMAB KIT

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Pembrolizumab + Trametinib

Indication/Tumor Type melanoma

Response Type no benefit

Publications:

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)

Abdou Y et al., 2019, Combination of pembrolizumab and imatinib in a patient with double KIT mutant melanoma: A case report., Medicine (Baltimore)

CYTARABINE KIT

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dasatinib + Cytarabine

Indication/Tumor Type acute myeloid leukemia

Response Type sensitive

Publications:

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.
INFIGRATINIB KIT

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy BGJ398 + Imatinib

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Publications:

Li et al., 2015, FGFR-Mediated Reactivation of MAPK Signaling Attenuates Antitumor Effects of Imatinib in Gastrointestinal Stromal Tumors., Cancer Discov

GILTERITINIB KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type decreased response

Indication/Tumor Type acute myeloid leukemia

Evidence Type Actionable

Publications:

Weisberg E et al., 2019, Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignancies., Br J Haematol

LETROZOLE KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Phase 0

Response Type predicted - sensitive

Publications:

Chow LW et al., 2008, Evaluation of neoadjuvant inhibition of aromatase activity and signal transduction in breast cancer., Cancer Lett

GZD-824 DIMESYLATE KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type sensitive

Publications:

Liu X et al., 2019, Preclinical development of HQP1351, a multikinase inhibitor targeting a broad spectrum of mutant KIT kinases, for the treatment of imatinib-resistant gastrointestinal stromal tumors., Cell Biosci

CRIZOTINIB KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Case Reports/Case Series

Response Type predicted - resistant

Publications:

McCoach CE et al., 2018, Resistance Mechanisms to Targeted Therapies in ROS1+ and ALK+ Non-small Cell Lung Cancer., Clin Cancer Res

Katayama et al., 2012, Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers., Sci Transl Med

DERAZANTINIB KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical - Cell culture

Publications:

Hall TG et al., 2016, Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation., PLoS One
ENTRECTINIB KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
BARASERTIB KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL578061 KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
GW843682X KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL327127 KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL541400 KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
JNJ-7706621 KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CYC-116 KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
AMG-191 KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
chembl:CHEMBL574059 KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
ROMIPLOSTIM KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
SP-600125 KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
SNS-314 KIT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

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:

GuideToPharmacologyGenes: 1805

Version: 4-March-2015

Alternate Names:

v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog HUGO Gene Name

6342 HUGO Gene ID

KIT Gene Symbol

Gene Info:

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

GuideToPharmacology Gene Category ID 322

GuideToPharmacology Gene Type catalytic_receptor

Gene Categories:

KINASE, TYROSINE 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:

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

JAX-CKB: KIT

Version: 15-September-2020

Alternate Names:

3815 CKB Entrez Id

KIT CKB Gene Synonym

C-Kit CKB Gene Synonym

Gene Info:

Publications:

Banks E et al., 2020, Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors., Sci Transl Med

Poveda et al., 2014, GEIS 2013 guidelines for gastrointestinal sarcomas (GIST)., Cancer Chemother. Pharmacol.

Nishida et al., 2016, The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines., Gastric Cancer

DrugBank: BE0000453

Version: 5.1.7

Alternate Names:

KIT DrugBank Gene Name

P10721 UniProt Accession

3815 Entrez Gene Id

Gene Info:

Publications:

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

Dizdar et al., 2008, Dasatinib may also inhibit c-Kit in triple negative breast cancer cell lines., Breast Cancer Res. Treat.

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.

DoCM: KIT

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

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

MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn

Smith et al., 2012, Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia., Nature

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.

CGI: KIT

Version: 14-September-2020

Alternate Names:

Gene Info:

Publications:

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.

Cauchi et al., 2012, Evaluation of nilotinib in advanced GIST previously treated with imatinib and sunitinib., Cancer Chemother. Pharmacol.

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:
GuideToPharmacologyInteractions: ENSG00000157404
- Version: 20-July-2020
Alternate Names:

KIT proto-oncogene, receptor tyrosine kinase GuideToPharmacology Name

P10721 UniProtKB ID

Gene Info:

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

KIT TTD Gene Abbreviation

T57700 TTD Target ID

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:

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

Gene Info:

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

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:

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

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

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

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

Reported Cancer Type	Melanoma
Clinical Status	preclinical
Clinical Status	early trials

Response Type	decreased response
Approval Status	Preclinical - Cell culture
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	axitinib, AG-013736
Novel drug target	Established target
Reported Cancer Type	Prostate

Notes
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

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

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

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

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

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

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

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

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

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

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

KIT Gene Record

KIT 3815 Druggable GenomeClinically Actionable

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

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

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

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications: Kim et al., 2014, Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal stromal tumor., Clin. Cancer Res. Cannarile MA et al., 2017, Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy., J Immunother Cancer

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

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

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications: Caenepeel et al., 2010, Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors., J. Exp. Clin. Cancer Res.

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

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

Interaction Types & Directionality: inhibitor (inhibitory)

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

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

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications: Liu F et al., 2019, Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors., Ther Adv Med Oncol

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications: Sonpavde et al., 2007, Pazopanib: a novel multitargeted tyrosine kinase inhibitor., Curr Oncol Rep

Interaction Types & Directionality: inhibitor (inhibitory)

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

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications: Zhao et al., 2014, Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants., Cancer Sci.

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

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

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

Interaction Types & Directionality: inhibitor (inhibitory)

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

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

Publications: Mahadevan et al., 2007, A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors., Oncogene

Interaction Types & Directionality: inhibitor (inhibitory)

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

Interaction Types & Directionality: inhibitor (inhibitory)

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

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

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

Publications:

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Stem cell growth factor receptor inhibitor Novel drug target Established target

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Drug family Pan-TK inhibitor

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

Alteration KIT:D820E

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

Publications:

Kim et al., 2014, Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal stromal tumor., Clin. Cancer Res.

Cannarile MA et al., 2017, Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy., J Immunother Cancer

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Indication/Tumor Type mast-cell leukemia

Response Type predicted – sensitive

Approval Status Preclinical - Patient cell culture

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Notes

Publications:

Caenepeel et al., 2010, Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors., J. Exp. Clin. Cancer Res.

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Clinical Status preclinical

Clinical Status early trials

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Response Type decreased response

Approval Status Preclinical - Cell culture

Approval Status Phase II

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name axitinib, AG-013736

Novel drug target Established target

Reported Cancer Type Prostate

Publications:

Liu F et al., 2019, Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors., Ther Adv Med Oncol

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Publications:

Sonpavde et al., 2007, Pazopanib: a novel multitargeted tyrosine kinase inhibitor., Curr Oncol Rep

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Preclinical

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Publications:

Zhao et al., 2014, Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants., Cancer Sci.

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

Indication/Tumor Type melanoma

Response Type sensitive

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type sensitive

Approval Status Phase I

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

Publications:

Mahadevan et al., 2007, A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors., Oncogene

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type gastrointestinal stromal tumor

Response Type predicted – sensitive

Approval Status Phase I

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

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

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand Inhibition

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Novel drug target Established target

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? True

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Stem cell growth factor receptor inhibitor

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name vatalanib, PTK 787

Novel drug target Established target

Trial Name Vatalanib

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Stem cell growth factor receptor inhibitor

Direct Interaction yes

Notes

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

Evidence Type	Actionable
Approval Status	Clinical Study
Response Type	no benefit

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

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

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

Indication/Tumor Type	Advanced Solid Tumor
Response Type	sensitive
Approval Status	Preclinical - Cell culture

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

v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog	HUGO Gene Name
6342	HUGO Gene ID
KIT	Gene Symbol

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