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. Bafetinibinhibits 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. In 2005, the compound was licensed to Innovive Pharmaceuticals (acquired by CytRx Oncology in 2008) by Nippon Shinyaku on a worldwide basis, with the exception of Japan, for the treatment of CML. Orphan drug designation was assigned to the compound for the treatment of CML in the U.S in 2007 and in the E.U. in 2010. Bafetinib is in phase II for the treatment of hormone-refractory prostate cancer and chronic lymphocytic leukemia.