Open AccessSensitivity of human cells bearing oncogenic mutant kit isoforms to the novel tyrosine kinase inhibitor INNO‐406
Author(s) -
Pan Jingxuan,
QuintásCardama Alfonso,
Manshouri Taghi,
Cortes Jorge,
Kantarjian Hagop,
Verstovsek Srdan
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00516.x
Subject(s) - gene isoform , mutant , tyrosine kinase , tyrosine kinase inhibitor , kinase , microbiology and biotechnology , bruton's tyrosine kinase , biology , cancer research , chemistry , biochemistry , signal transduction , gene , genetics , cancer
The activity of the novel tyrosine kinase inhibitor INNO‐406 against human cells with mutated KIT was investigated. Human mast cell (HMC)‐1.1 cells with juxtamembrane domain mutation V560G, and HMC‐1.2 cells with both V560G and the kinase domain mutation D816V, were treated with INNO‐406 (0.02–5.00 µM) or imatinib for 72 h. INNO‐406 and imatinib were equipotent against HMC‐1 cells regarding cell proliferation (IC 50 51 nM and 75 nM, respectively), inhibition of KIT phosphorylation, and induction of apoptosis. In contrast, neither drug was effective against HMC‐1.2 cells at the dose range tested. The present results suggest clinical potential for INNO‐406 in KIT V560G‐expressing malignancies. ( Cancer Sci 2007; 98: 1223–1225)