Baricitinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Baricitinib (LY3009104, INCB028050) 是一种选择性 JAK1 和 JAK2 抑制剂，在无细胞测定中 IC50 分别为 5.9 nM 和 5.7 nM。

Baricitinib (LY3009104, INCB028050) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. Phase 3.(In Vitro):In cell-based assays, Baricitinib (INCB028050) proves to be a potent inhibitor of JAK signaling and function. In PBMCs, Baricitinib inhibits IL-6-stimulated phosphorylation of the canonical substrate STAT3 (pSTAT3) and subsequent production of the chemokine MCP-1 with IC50 values of 44 nM and 40 nM, respectively. In isolated naive T-cells, INCB028050 also inhibits pSTAT3 stimulated by IL-23 (IC50=20 nM). Importantly, this inhibition prevented the production of two pathogenic cytokines (IL-17 and IL-22) produced by Th17 cells-a subtype of helper T cells with demonstrable inflammatory and pathogenic properties-with an IC50 value of 50 nM. In stark contrast, the structurally similar but ineffective JAK1/2 inhibitors INCB027753 and INCB029843 has no significant effect in any of these assays systems when tested at concentrations up to 10 μM. (In Vivo):Baricitinib (INCB028050) treatment, compares with vehicle, inhibits the increase in hind paw volumes during the 2 wk of treatment by 50% at a dose of 1 mg/kg and >95% at doses of 3 or 10 mg/kg. Because baseline paw volume measurements are taken on treatment day 0-in animals with significant signs of disease-it is possible to have >100% inhibition in animals showing marked improvement in swelling. Baricitinib (0.7 mg/day) treated mice exhibits substantially reduced inflammation as assessed by H&E staining, reduced CD8 infiltration, and reduced MHC class I and class II expression when compared with vehicle-control treated mice. CD8+NKG2D+ cells, critical effectors of disease in murine and human alopecia areata (AA), are greatly diminished in Baricitinib treated mice compare with vehicle control treated mice.

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LY3009104, INCB028050

Angiogenesis

Chk

Chk2| JAK1| JAK2| JAK3| Tyk2

Inflammation/Immunology

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1187594-09-7

371.42

C16H17N7O2S

>98% (HPLC)

DMSO: 74 mg/mL (199.23 mM)

CCS(=O)(=O)N1CC(CC#N)(C1)N1C=C(C=N1)C1=C2C=CNC2=NC=N1

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(-20℃)

With Ice Pack

≥ 2 years