Ruxolitinib sulfate (INCB018424 sulfate) is a potent, selective JAK1/2 inhibitor with IC 50 s of 3.3 nM/2.8 nM. Ruxolitinib sulfate shows > 130-fold selectivity for JAK1/2 versus JAK3.

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) demonstrates over a 90% survival rate by day 22 and significantly reduces splenomegaly and inflammatory cytokine levels in a JAK2V617F-driven mouse model; it effectively targets and eradicates neoplastic cells without causing myelosuppression or immunosuppression [1]. In myelofibrosis patients within a double-blind trial, 41.9% achieved the primary endpoint with Ruxolitinib treatment versus only 0.7% in the placebo group, highlighting its efficacy in spleen volume reduction and symptom improvement [2]. Furthermore, 28% of patients receiving Ruxolitinib (15 mg twice daily) experienced at least a 35% decrease in spleen volume by week 48, a stark contrast to none in the best available therapy group, accompanied by a 56% reduction in mean palpable spleen length versus a 4% increase with alternative treatments. Ruxolitinib also significantly enhances overall quality-of-life and reduces myelofibrosis symptoms [3].