Sensitivity of human cells bearing oncogenic mutant kit isoforms to the novel tyrosine kinase inhibitor INNO-406

Jingxuan Pan, Alfonso Quintás-Cardama, Taghi Manshouri, Jorge Cortes, Hagop Kantarjian, Srdan Verstovsek

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1223-1225
Number of pages3
JournalCancer Science
Volume98
Issue number8
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

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Protein-Tyrosine Kinases
Protein Isoforms
Mast Cells
Mutation
Inhibitory Concentration 50
Phosphotransferases
Phosphorylation
Cell Proliferation
bafetinib
Apoptosis
Pharmaceutical Preparations
Neoplasms
Imatinib Mesylate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Sensitivity of human cells bearing oncogenic mutant kit isoforms to the novel tyrosine kinase inhibitor INNO-406. / Pan, Jingxuan; Quintás-Cardama, Alfonso; Manshouri, Taghi; Cortes, Jorge; Kantarjian, Hagop; Verstovsek, Srdan.

In: Cancer Science, Vol. 98, No. 8, 01.08.2007, p. 1223-1225.

Research output: Contribution to journalArticle

Pan, Jingxuan ; Quintás-Cardama, Alfonso ; Manshouri, Taghi ; Cortes, Jorge ; Kantarjian, Hagop ; Verstovsek, Srdan. / Sensitivity of human cells bearing oncogenic mutant kit isoforms to the novel tyrosine kinase inhibitor INNO-406. In: Cancer Science. 2007 ; Vol. 98, No. 8. pp. 1223-1225.
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