CEP-701 is a JAK2 Inhibitor Which Attenuates JAK2/STAT5 Signaling Pathway and the Proliferation of Primary Cells from Patients with Myeloproliferative Disorders.
Blood(2006)
摘要
Small molecule tyrosine kinase inhibitors have had dramatic clinical efficacy in chronic myelogenous leukemia. The identification of a specific activating mutation (V617F) in the gene encoding Janus Kinase 2 (JAK2) in a large proportion of patients with myeloproliferative disorders (MPDs) suggests that a kinase inhibitor might have similar clinical utility. CEP-701 is an orally-active inhibitor of receptor tyrosine kinases including FLT-3, and is currently in phase II clinical trials in acute myeloid leukemia (AML) for patients with FLT-3 mutations. The ability of CEP-701 to inhibit JAK2 and suppress the growth of cells from patients with MPDs was evaluated. In in vitro kinase assay CEP-701 inhibited wild type JAK2 (IC50 l nM). In addition, CEP-701 inhibited:
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