Dasatinib, a multi‐targeted tyrosine kinase inhibitor with a different selectivity profile than imatinib, does not display cardiotoxicological potential in neonatal rat cardiomyocytes.

Imatinib, a tyrosine kinase inhibitor (TKI) indicated for chronic myelogenous leukemia (CML), is reportedly associated with congestive heart failure. Mitochondrial abnormalities were reported from both imatinib‐treated mice and CML patients with CHF, which correlated with mitochondrial membrane potential loss, reduced cell viability, and increased apoptosis in imatinib treated rat cardiomyocytes in vitro (Kerkela, Nat. Med . 2006). Dasatinib, a TKI with a different kinase selectivity profile than imatinib, is also approved for use in CML patients. It was postulated that ABL kinase inhibition is responsible for imatinib cardiotoxicity, and since dasatinib is a more potent ABL inhibitor than imatinib (0.045 versus 24 nM BCR‐ABL K i , respectively), the in vitro cardiotoxicological potential of these drugs at pharmacologically relevant concentrations (0.09 and 50 μM, respectively) was investigated in primary rat cardiomyocytes. Dasatinib did not significantly affect mitochondrial membrane potential, cell viability, apoptosis, or cellular ultrastructure in vitro , whereas imatinib significantly affected these parameters. Results suggest that at pharmacologically relevant concentrations, dasatinib does not induce cardiotoxicity, as does imatinib. Proteomic profiling of dasatinib and imatinib treated cardiomyocytes may delineate molecular mechanisms behind differences in cardiotoxic potential.