Brief Description

Ruxolitinib(INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM, >130-fold selectivity for JAK1/2 versus JAK3.
IC50 value: 3.3 nM/2.8 nM(JAK1/JAK2)
Target: JAK1/2
in vitro: INCB018424 potently and selectively inhibits JAK2V617F-mediated signaling and proliferation in Ba/F3 cells and HEL cells. INCB018424 markedly increases apoptosis in a dose dependent manner in Ba/F3 cells. INCB018424 (64 nM) results in a doubling of cells with depolarized mitochondria in Ba/F3 cells. INCB018424 inhibits proliferating of erythroid progenitors from normal donors and polycythemia vera patients with IC50 of 407 nM and 223 nM, respectively. INCB018424 demonstrates remarkable potency against erythroid colony formation with IC50 of 67 nM.
in vivo: INCB018424 (180 mg/kg, orally, twice a day) results in survive rate of greater than 90% by day 22 in a JAK2V617F-driven mouse model. INCB018424 (180 mg/kg, orally, twice a day) 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. The primary end point is reached in 41.9% of patients in the Ruxolitinib group 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.

Solubility

DMSO 60 mg/mL; Water <1 mg/mL; Ethanol 60 mg/mL

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

White to off-white solid