CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms.
Jeffrey W Tyner, Thomas G Bumm, Jutta Deininger, Lisa Wood, Karl J Aichberger, Marc M Loriaux, Brian J Druker, Christopher J Burns, Emmanuelle Fantino, Michael W Deininger
Blood | Published : 2010
Activating alleles of Janus kinase 2 (JAK2) such as JAK2(V617F) are central to the pathogenesis of myeloproliferative neoplasms (MPN), suggesting that small molecule inhibitors targeting JAK2 may be therapeutically useful. We have identified an aminopyrimidine derivative (CYT387), which inhibits JAK1, JAK2, and tyrosine kinase 2 (TYK2) at low nanomolar concentrations, with few additional targets. Between 0.5 and 1.5muM CYT387 caused growth suppression and apoptosis in JAK2-dependent hematopoietic cell lines, while nonhematopoietic cell lines were unaffected. In a murine MPN model, CYT387 normalized white cell counts, hematocrit, spleen size, and restored physiologic levels of inflammatory cy..View full abstract
Awarded by NHLBI NIH HHS
Awarded by NINR NIH HHS