Nilotinib-resistant KIT mutants do not bind nilotinib

Stable Identifier
Reaction [transition]
Homo sapiens
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A number of secondary mutations that arise in mutated KIT receptors confer resistance to nilotinib. This is particularly true for the 'gate-keeper' mutation T760I that increases the affinity of the receptor for ATP, rendering it less susceptible to ATP-competitive inhibitors (Kissova et al, 2016; Serrano et al, 2019; Guo et al, 2007; Roberts et al, 2007; reviewed in Klug et al, 2018; Roskoski, 2018).
Literature References
PubMed ID Title Journal Year
17699867 Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor

Hom, G, Antonescu, CR, Guo, T, Agaram, NP, Veach, D, Singer, S, Schwartz, GK, Besmer, P, Maki, RG, Clarkson, BD, D'Adamo, D, Wong, GC, DeMatteo, RP

Clin. Cancer Res. 2007
17363509 Resistance to c-KIT kinase inhibitors conferred by V654A mutation

Griffith, R, Odell, AF, Roberts, KG, Baleato, RM, Lyons, AB, Ashman, LK, Byrnes, EM

Mol. Cancer Ther. 2007
29704617 The role of small molecule Kit protein-tyrosine kinase inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
30792533 Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours

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

Br. J. Cancer 2019
29964125 Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases

Heinrich, MC, Kent, JD, Klug, LR

Pharmacol. Ther. 2018
27527414 The human tyrosine kinase Kit and its gatekeeper mutant T670I, show different kinetic properties: Implications for drug design

Maga, G, Crespan, E, Kissova, M

Bioorg. Med. Chem. 2016
Normal reaction
Functional status

Loss of function of nilotinib resistant KIT mutants [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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