TY - JOUR
T1 - Sensitivity of human cells bearing oncogenic mutant kit isoforms to the novel tyrosine kinase inhibitor INNO-406
AU - Pan, Jingxuan
AU - Quintás-Cardama, Alfonso
AU - Manshouri, Taghi
AU - Cortes, Jorge
AU - Kantarjian, Hagop
AU - Verstovsek, Srdan
PY - 2007/8
Y1 - 2007/8
N2 - 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 (IC50 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.
AB - 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 (IC50 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.
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U2 - 10.1111/j.1349-7006.2007.00516.x
DO - 10.1111/j.1349-7006.2007.00516.x
M3 - Article
C2 - 17517053
AN - SCOPUS:34347253239
SN - 1347-9032
VL - 98
SP - 1223
EP - 1225
JO - Cancer Science
JF - Cancer Science
IS - 8
ER -