Ruxolitinib

A potent, selective, orally active JAK1/JAK2 inhibitor with IC50 of 3.3/2.8 nM, respectively; displays modest selectivity against Tyk2 (6-fold) and marked selectivity (>130-fold) against JAK3; inhibits IL-6 signaling (IC50=281 nM), and proliferation of JAK2V617F(+) Ba/F3 cells (IC50=127 nM); suppresses erythroid progenitor colony formation from JAK2V617F(+) polycythemia vera patients (IC50=67 nM) in primary cultures; markedly reduces level of inflammatory cytokines, and preferentially eliminates neoplastic cells in a mouse model of JAK2V617F(+) MPN.Bone Cancer Approved(In Vitro):Ruxolitinib 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 IC50 of 67 nM, and inhibits proliferating of erythroid progenitors from normal donors and polycythemia vera patients with IC50 values of 407 nM and 223 nM, respectively.(In Vivo):Ruxolitinib (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.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.