Ruxolitinib sulfate (INCB018424 sulfate) is a potent, selective inhibitor of JAK1/2 with IC50 values of 3.3 nM/2.8 nM, demonstrating over 130-fold selectivity for JAK1/2 compared to JAK3.

JAK2:2.8 nM, JAK1:3.3 nM, JAK3:428 nM, Tyk2:19 nM

Ruxolitinib sulfate (INCB018424 sulfate) effectively and selectively hampers JAK2V617F-mediated signaling and cell growth, significantly boosts apoptosis in a dose-dependent manner, and achieves a twofold increase in cells with depolarized mitochondria at a concentration of 64 nM in Ba/F3 cells. It also exhibits exceptional efficacy in inhibiting erythroid colony formation, noted by an IC50 of 67 nM. Moreover, it suppresses the proliferation of erythroid progenitors from both healthy individuals and patients with polycythemia vera, as evidenced by IC50 values of 407 nM and 223 nM, respectively [1].

Ruxolitinib (INCB018424 sulfate; 180 mg/kg, orally, twice daily) achieves over a 90% survival rate by day 22 and significantly reduces splenomegaly and inflammatory cytokine levels in a JAK2V617F-driven mouse model, effectively targeting and eradicating neoplastic cells without causing myelosuppression or immunosuppression [1]. In myelofibrosis patients within a double-blind trial, 41.9% reached the primary endpoint with Ruxolitinib treatment compared to 0.7% in the placebo group, demonstrating its efficacy in reducing spleen volume and improving symptoms [2]. Additionally, 28% of patients receiving Ruxolitinib (15 mg twice daily) experienced at least a 35% reduction in spleen volume by week 48, a stark contrast to none in the best available therapy group, with a 56% reduction in mean palpable spleen length versus a 4% increase with alternative treatments. Ruxolitinib also significantly improves overall quality of life and reduces myelofibrosis symptoms [3].