Bcr-Abl, a fusion protein with deregulated tyrosine kinase activity, is highly expressed in chronic myelogenous leukemia (CML). Bafetinib 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 (IC50 = 5.8 nM).1 It is 25- to 55-fold more potent than imatinib in vitro and ≥10-fold more potent in vivo.1 Bafetinib inhibits 12 out of the 13 most frequent imatinib-resistant Bcr-Abl point mutations, but not the T315I mutation and also targets the Src family kinase Lyn (IC50 = 19 nM), which has been associated with resistance to imatinib in CML.1
1.Kimura, S., Naito, H., Segawa, H., et al.NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemiaBlood106(12)3948-3954(2005)