Bafetinib, a dual Bcr-Abl/Lyn tyrosine kinase inhibitor for the potential treatment of leukemia

Fabio P.S. Santos, Hagop Kantarjian, Jorge Cortes, Alfonso Quintas-Cardama

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Bafetinib (NS-187, INNO-406) is a second-generation tyrosine kinase inhibitor in development by CytRx under license from Nippon Shinyaku for treating Bcr-Abl+ leukemia's, including chronic myelogenous leukemia (CML) and Philadelphia+ acute lymphoblastic leukemia. It is a rationally developed tyrosine kinase inhibitor based on the chemical structure of imatinib, with modifications added to improve binding and potency against Bcr-Abl kinase. Besides Abl, bafetinib targets the Src family kinase Lyn, which has been associated with resistance to imatinib in CML. In preclinical studies, bafetinib was 25-to 55-fold more potent than imatinib in vitro and 10-fold more potent in vivo. Bafetinib inhibits 12 of the 13 most frequent imatinib-resistant Bcr-Abl point mutations, but not a Thr315Ile mutation. A small fraction of bafetinib crosses the blood-brain barrier, reaching brain concentrations adequate for suppression of Bcr-Abl+ cells. Data from a phase I clinical trial conducted in patients with imatinib-resistant or-intolerant CML have confirmed that bafetinib has clinical activity in this setting, inducing a major cytogenetic response in 19% of those patients in chronic phase. Currently, bafetinib is being developed in two phase II clinical trials for patients with B-cell chronic lymphocytic leukemia and prostate cancer, and a trial is in progress for patients with brain tumors.

Original languageEnglish (US)
Pages (from-to)1450-1465
Number of pages16
JournalCurrent Opinion in Investigational Drugs
Issue number12
StatePublished - Dec 2010
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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