Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC₅₀a of 11 nM and 18 nM,respectively. CYT387 shows much less activity against JAK3.

Momelotinib (CYT387) inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC₅₀ of 1400 nM. Furthermore, Momelotinib (CYT387) 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 (CYT387) 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. Momelotinib (CYT387) inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, Momelotinib (CYT387) induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies PS-341 and L-PAM in primary multiple myeloma (MM) cells.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

In a murine MPN model, Momelotinib (CYT387) normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

In a murine MPN model, Momelotinib (CYT387) normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Pardanani A, et al. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia, 2009, 23(8), 1441-1445.  [Content Brief]

  . Monaghan KA, et al. The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells. Leukemia, 2011, 25(12), 1891-1899.  [Content Brief]

  . Tyner JW, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood, 2010, 115(25), 5232-5240.  [Content Brief]

  [4]. Kitajima S, et al.Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS.Cancer Cell. 2018 Sep 10;34(3):439-452.e6.  [Content Brief]