Momelotinib (mesylate)

Momelotinib mesylate (CYT387 mesylate) is an ATP-competitive inhibitor of JAK1/JAK2 with IC₅₀ of 11 nM/18 nM, appr 10-fold selectivity versus JAK3. IC50 & Target:IC50: 11 nM (JAK1), 18 nM (JAK2)^[1] In Vitro: Momelotinib mesylate is an inhibitor of JAK1/JAK2 with IC₅₀ of 11 nM/18 nM, appr 10-fold selectivity versus JAK3. Momelotinib inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC₅₀ of 1400 nM. Furthermore, Momelotinib also causes the inhibition of cell proliferation in cell lines constitutively activated by JAK2 or MPL signaling, including Ba/F3-MPLW515L cells, CHRF-288-11 cells and Ba/F3-TEL-JAK2 cells with IC₅₀ of 200 nM, 1 nM and 700 nM, respectively. In addition, Momelotinib has been shown to inhibit erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC₅₀ of 2 μM-4 μM^[1]. Momelotinib inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, Momelotinib induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies bortezomib and melphalan in primary multiple myeloma (MM) cells^[2]. In Vivo: In a murine MPN model, Momelotinib normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines^[3].