KIT mutants bind type I TKIs

Stable Identifier
R-HSA-9669898
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Dovitinib inhibits the growth of primary exon 11 mutations in GIST cell lines, with IC50 values of less than 500. Dovitinib is also active against the exon 13 mutation K654A and the exon 14 mutation T670I, but is inactive against mutations in exon 17 and 18, encoding the KIT activation loop (Serrano et al, 2019). Midostaurin inhibits the activity of KIT receptors with mutations in the juxtamembrane domain as well as those in the ATP-binding cleft and activation loop domains (Growney et al, 2005; Gleixner et al, 2006; Gotlib et al, 2016; Weisberg et al, 2019; Gebreyohannes et al, 2019). Avapritinib is a more selective KIT inhibitor that is active against activation loop mutants (Evans et al, 2017; Weisberg et al, 2019).

Literature References
PubMed ID Title Journal Year
31309543 Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignancies

Weisberg, E, Meng, C, Case, AE, Sattler, M, Tiv, HL, Gokhale, PC, Buhrlage, SJ, Liu, X, Yang, J, Wang, J, Gray, N, Stone, RM, Adamia, S, Dubreuil, P, Letard, S, Griffin, JD

Br. J. Haematol. 2019
30274985 Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal Tumors

Gebreyohannes, YK, Wozniak, A, Zhai, ME, Wellens, J, Cornillie, J, Vanleeuw, U, Evans, E, Gardino, AK, Lengauer, C, Debiec-Rychter, M, Sciot, R, Schöffski, P

Clin. Cancer Res. 2019
30792533 Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours

Serrano, C, Mariño-Enríquez, A, Tao, DL, Ketzer, J, Eilers, G, Zhu, M, Yu, C, Mannan, AM, Rubin, BP, Demetri, GD, Raut, CP, Presnell, A, McKinley, A, Heinrich, MC, Czaplinski, JT, Sicinska, E, Bauer, S, George, S, Fletcher, JA

Br. J. Cancer 2019
29093181 A precision therapy against cancers driven by KIT/PDGFRA mutations

Evans, EK, Gardino, AK, Kim, JL, Hodous, BL, Shutes, A, Davis, A, Zhu, XJ, Schmidt-Kittler, O, Wilson, D, Wilson, K, DiPietro, L, Zhang, Y, Brooijmans, N, LaBranche, TP, Wozniak, A, Gebreyohannes, YK, Schöffski, P, Heinrich, MC, Deangelo, DJ, Miller, S, Wolf, B, Kohl, N, Guzi, T, Lydon, N, Boral, A, Lengauer, C

Sci Transl Med 2017
16189265 PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects

Gleixner, KV, Mayerhofer, M, Aichberger, KJ, Derdak, S, Sonneck, K, Böhm, A, Gruze, A, Samorapoompichit, P, Manley, PW, Fabbro, D, Pickl, WF, Sillaber, C, Valent, P

Blood 2006
15972446 Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation

Gotlib, J, Berubé, C, Growney, JD, Chen, CC, George, TI, Williams, C, Kajiguchi, T, Ruan, J, Lilleberg, SL, Durocher, JA, Lichy, JH, Wang, Y, Cohen, PS, Arber, DA, Heinrich, MC, Neckers, L, Galli, SJ, Gilliland, DG, Coutré, SE

Blood 2005
15790786 Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412

Growney, JD, Clark, JJ, Adelsperger, J, Stone, R, Fabbro, D, Griffin, JD, Gilliland, DG

Blood 2005
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
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