Nilotinib: A phenylamino-pyrimidine derivative with activity against BCR-ABL, KIT and PDGFR kinases

Alfonso Quintás-Cardama, Jorge Cortes

Research output: Contribution to journalReview article

Abstract

The BCR-ABL kinase inhibitor imatinib mesylate is currently the standard therapy for patients with chronic myeloid leukemia (CML). However, mutations within the ABL kinase domain interfering with drug binding have been identified as the main mechanism of resistance to imatinib. Multiple distinct BCR-ABL kinase mutant isoforms conferring varying degrees of resistance to tyrosine kinase inhibitors have been reported. Nilotinib is a tyrosine kinase inhibitor 30-fold more potent than imatinib against BCR-ABL kinase. Nilotinib is active against a wide range of imatinib-resistant BCR-ABL mutant isoforms, except for T3151. Results from Phase II studies of nilotinib for patients with CML after failure or intolerance to imatinib therapy have shown a favorable toxicity profile and confirmed the high efficacy of nilotinib in this setting. Studies addressing the activity of nilotinib in newly-diagnosed patients with CML are underway. Furthermore, nilotinib is a potent inhibitor of KIT and PIDGFR kinases. Here, we review the preclinical development of nilotinib and the activity of this agent in patients with CML and in tumors driven by KIT and/or PDGFR mutant kinases, such as gastrointestinal stromal tumors and some forms of clonal hypereosinophilia.

Original languageEnglish (US)
Pages (from-to)611-621
Number of pages11
JournalFuture Oncology
Volume4
Issue number5
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

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Phosphotransferases
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Protein Isoforms
Gastrointestinal Stromal Tumors
Proxy
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
pyrimidine
Imatinib Mesylate
Mutation
Therapeutics
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nilotinib : A phenylamino-pyrimidine derivative with activity against BCR-ABL, KIT and PDGFR kinases. / Quintás-Cardama, Alfonso; Cortes, Jorge.

In: Future Oncology, Vol. 4, No. 5, 01.10.2008, p. 611-621.

Research output: Contribution to journalReview article

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