Baricitinib 是一种选择性，可口服的JAK1和JAK2抑制剂，IC50分别为5.9 nM 和 5.7 nM，具有潜在的抗炎、免疫调节和抗肿瘤活性。

Baricitinib is an orally bioavailable inhibitor of Janus kinases 1 and 2 (JAK1/2), with potential anti-inflammatory, immunomodulating and antineoplastic activities.

在佐剂性关节炎大鼠模型中Baricitinib（10 mg / kg口服）可抑制JAK1 / 2信号传导,同时抑制免疫浸润.在CIA和CAIA模型中,Baricitinib（10 mg / kg）改善软骨损伤和炎症,抑制迟发型超敏反应.

在分离的未成熟型T 细胞中（IC50=20 nM）,Baricitinib抑制IL-23刺激的STAT3的磷酸化。在外周血单核细胞中,Baricitinib抑制IL-6刺激底物STAT3的磷酸化（IC50=44 nM）以及随后趋化因子MCP-1（IC50=40 nM）的产生。

Enzyme assays are performed using a homogeneous time-resolved fluorescence assay with recombinant epitope tagged kinase domains (JAK1, 837-1142; JAK2, 828-1132; JAK3, 718-1124; Tyk2, 873-1187) or full-length enzyme (cMET and Chk2) and peptide substrate. Each enzyme reaction is performed with or without test compound (11-point dilution), JAK, cMET, or Chk2 enzyme, 500 nM (100 nM for Chk2) peptide, ATP (at the Km specific for each kinase or 1 mM), and 2.0% DMSO in assay buffer. The calculated IC50 value is the compound concentration required for inhibition of 50% of the fluorescent signal. Additional kinase assays are performed at Cerep using standard conditions at 200 nM. Enzymes tested included: Abl, Akt1, AurA, AurB, CDC2, CDK2, CDK4, CHK2, c-kit, EGFR, EphB4, ERK1, ERK2, FLT-1, HER2, IGF1R, IKKα, IKKβ, JNK1, Lck, MEK1, p38α, p70S6K, PKA, PKCα, Src, and ZAP70[1].

Baricitinib(INCB 028050) is dissolved in stock solutions, and then diluted with appropriate media before use[1]. Human PBMCs are isolated by leukapheresis followed by Ficoll-Hypaque centrifugation. For the determination of IL-6-induced MCP-1 production, PBMCs are plated at 3.3×105 cells per well in RPMI 1640+10% FCS in the presence or absence of various concentrations of INCB028050 (1 nM, 10 nM, 100 nM, 1 μM, and 10 μM). Following preincubation with compound for 10 min at room temperature, cells are stimulated by adding 10 ng/mL human recombinant IL-6 to each well. Cells are incubated for 48 h at 37°C, 5% CO2. Supernatants are harvested and analyzed by ELISA for levels of human MCP-1. The ability of INCB028050 to inhibit IL-6-induced secretion of MCP-1 is reported as the concentration required for 50% inhibition (IC50). Proliferation of Ba/F3-TEL-JAK3 cells is performed over 3 d using Cell-Titer Glo[1].

1187594-09-7

C16H17N7O2S

371.42

INCB028050;巴瑞克替尼;LY3009104

H2O:<1 mgml
DMSO:69 mg/mL (185.8 mM)
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years