MK0457 + dasatinib

MK0457 + dasatinib is an experimental **combination therapy** of two small molecules with distinct kinase inhibition profiles, designed primarily for the treatment of **Philadelphia chromosome-positive leukemias**, including those harboring the T315I BCR-ABL mutation, which confers resistance to many standard therapies. **MK0457** (VX-680) is a pan-Aurora kinase inhibitor that also targets mutant BCR-ABL forms including T315I; **dasatinib** is a broad-spectrum **tyrosine kinase inhibitor** that blocks BCR-ABL and Src-family kinases, approved as a monotherapy for CML and Ph+ ALL. The combinatorial approach enhances inhibition of leukemic cell proliferation, induces apoptosis (via greater PARP cleavage and caspase activation), and can overcome resistance seen with single-agent treatment, in both in vitro and in vivo models. The mechanism involves not only direct kinase inhibition but also suppression of downstream survival signals (such as phospho-Stat5) and activation of apoptosis pathways (notably p38 MAP kinase and MAPKAP Kinase-2).

Other names

VX-680VX680VX 680BMS-354825BMS354825BMS 354825