Baricitinib, Inhibitor

Baricitinib (LY3009104, INCB028050)

Cat. Num. AAA14579

• Purity: 98.9%
• Synonyms: Baricitinib; N/A; Baricitinib (LY3009104, INCB028050); Baricitinib phosphate; Baricitinib, inhibitor

• Purity/Purification: 98.9%
• Form/Format: POWDER

• CAS: 1187595-84-1
• Formula: C16H₂₀N₇O₆PS
• Solubility: DMSO 200
• Receptor (IC50: JAK 1 5.9 nM; JAK 2 5.7 nM; JAK3 >400 nM; Tyk 2 53 nM
• Animal Experiment: Rats
• Biological Activity: Baricitinib phosphate is a selective orally bioavailable JAK1/JAK2 inhibitor.
• Smiles: OP(=O)(O)O.CCS(=O)(=O)N1CC(CC#N)(C1)n1cc(cn1)c1c2cc[nH]c2ncn1
• In vitro Activity: 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 uM[1].
• In vivo Activity: 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[1]. 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[2].
• Kinase Assay: 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 (II-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, Aktl, AurA, AurB, CDC2, CDK2, CDK4, CHK2, c-kit, EGFR, EphB4, ERK1, ERK2, FLT-1, HER2, IGF1R, IKKo, IKK~, JNK1, Lck, MEK1, p380, p70S6K, PKA, PKCo, Src, and ZAP70[1].
• Cell Assay: Bariciti nib(INCB 028050) is dissolved in stock solutions, and then diluted withappropriate media before use[l]. 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 3.3x 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, 1IJM, and 10 IJM). 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 48h at 37°C, 5% CO2.
• Preparation and Storage: 2 years -80°C in solvent; 3 years -20°C in powder.

Structure