Ruxolitinib phosphate

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 (INCB018424) potently and selectively inhibits JAK2V617F-mediated signaling and proliferation. Ruxolitinib inhibits the growth of HEL cells with EC50 of 186 nM. Ruxolitinib markedly increases apoptosis in Ba/F3-EpoR-JAK2V617F cell system, and inhibits hematopoietic progenitor cell proliferation in primary MPN patient samples. (In Vivo) :Ruxolitinib (180 mg/kg, p.o.) reduces the tumor burden of mice inoculated with JAK2V617F-expressing cells without causing anemia or lymphopenia.