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.

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

Ruxolitinib sulfate (INCB018424 sulfate) potently and selectively inhibits JAK2V617F-mediated signaling and proliferation, markedly increases apoptosis in a dose dependent manner, and at 64 nM results in a doubling of cells with depolarized mitochondria in Ba/F3 cells. Ruxolitinib demonstrates remarkable potency against erythroid colony formation with IC 50 of 67 nM, and inhibits proliferating of erythroid progenitors from normal donors and polycythemia vera patients with IC 50 values of 407 nM and 223 nM, respectively [1].

Ruxolitinib (INCB018424 sulfate; 180 mg/kg, orally, twice a day) results in survive rate of greater than 90% by day 22 and markedly reduces splenomegaly and circulating levels of inflammatory cytokines, and preferentially eliminated neoplastic cells, resulting in significantly prolonged survival without myelosuppressive or immunosuppressive effects in a JAK2V617F-driven mouse model [1]. In the Ruxolitinib group, the primary end point is reached in 41.9% of patients, as compared with 0.7% in the placebo group in the double-blind trial of myelofibrosis. Ruxolitinib results in maintaining of reduction in spleen volume and improvement of 50% or more in the total symptom score [2]. Ruxolitinib (15 mg twice daily) treatment leads a total of 28% of the patients to have at least a 35% reduction in spleen volume at week 48 in patients with myelofibrosis, as compared with 0% in the group receiving the best available therapy. The mean palpable spleen length has decreased by 56% with Ruxolitinib but has increased by 4% with the best available therapy at week 48. Patients in the ruxolitinib group has an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis [3].