Momelotinib CAS# 1056634-68-4 莫洛替尼

Momelotinib is a potent, selective inhibitor of Janus kinases JAK1 and JAK2, as well as activin A receptor type I (ACVR1/ALK2). In vitro, it inhibits JAK1, JAK2, and ACVR1 with IC₅₀ values of 11 nM, 18 nM, and 15 nM, respectively, leading to effective blockade of STAT3 and STAT5 phosphorylation in cell-based assays (IC₅₀ ≈ 50–100 nM in Ba/F3 or HEL92.1.7 cells). Momelotinib also suppresses IL-6–induced STAT3 signaling in human cells with sub-100 nM potency. In vivo, oral administration of momelotinib significantly reduces splenomegaly, inflammatory cytokine levels, and aberrant myeloproliferation in JAK2V617F-driven mouse models of myelofibrosis and polycythemia vera, showing dose-dependent efficacy at 25–100 mg/kg/day. Additionally, in murine models of anemia of chronic disease, momelotinib improves hemoglobin and erythropoiesis through ACVR1 inhibition, which suppresses hepcidin production.