Baricitinib(INCB 028050; LY 3009104)是JAK1和JAK2抑制剂，IC50分别为5.9 nM和5.7 nM，比对JAK3和Tyk2的抑制性高70倍和10倍，对c-Met和Chk2无活性

Baricitinib的生物活性

Baricitinib(INCB 028050; LY 3009104) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2.
IC50 Value: JAK1 (5.9 nM) and JAK2 (5.7 nM) [1].
Target: JAK1/2
in vitro: INCB028050 inhibits intracellular signaling of multiple proinflammatory cytokines including IL-6 and IL-23 at concentrations <50 nM. Significant efficacy, as assessed by improvements in clinical, histologic and radiographic signs of disease, was achieved in the rat adjuvant arthritis model with doses of INCB028050 providing partial and/or periodic inhibition of JAK1/JAK2 and no inhibition of JAK3 [1].
in vivo: The efficacy following daily oral administration of INCB028050 was assessed at doses of 1, 3, or 10 mg/kg based on its pharmacokinetic profile in this species. Disease severity was assessed periodically, scoring clinical signs of disease. These doses were based on the PK/PD relationship established with the IL-6 WBA, with the goal of inhibiting JAK1/2 signaling by no more than 50% for half of the day. Relative to vehicle-treated animals, increasing doses of INCB028050 inhibited disease scores by 24% (p < 0.05), 57% (p < 0.01), and 81% (p < 0.01), respectively [1]. Baricitinib preferentially inhibits JAK1 and JAK2, with 10-fold selectivity over Tyk2 and 100-fold over JAK3. The observed effects of GLPG-0634 on the ACR20, albeit in a smaller study, appear to be at least as good as that seen with tofacitinib and superior to that of baricitinib, since baricitinib only moderately affect the ACR20 values in Phase IIa clinical studies [2].
Clinical trial: Baricitinib (LY3009104, INCB28050) against JAK1/JAK2 starting phase IIb for rheumatoid arthritis

化学信息

分子量	371.42	储存条件	参考CoA中推荐的条件进行储存。
分子式	C16H17N7O2S
CAS号	1187594-09-7
溶剂/溶解度	DMSO 74 mg/ml; water <1 mg/ml