Baricitinib phosphate

SKU: orb1305598

Description

Baricitinib phosphate

Research Area

Cardiovascular Research, Epigenetics & Chromatin, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1187595-84-1
• MW: 469.41
• Purity: 99.91%
• Formula: C₁₆H₂₀N₇O₆PS
• SMILES: OP(O)(O)=O.CCS(=O)(=O)N1CC(CC#N)(C1)n1cc(cn1)-c1ncnc2[nH]ccc12
• Target: Tyrosine Kinases,JAK
• Solubility: DMSO:50 mg/mL (106.52 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.26 mM)

Bioactivity

• Target IC50:
  JAK3:560 nM|Tyk2:53 nM|JAK2:5.7 nM|JAK1:5.9 nM
• In Vivo:
  Baricitinib (INCB028050) treatment significantly reduces hind paw swelling in comparison to the vehicle control, achieving a 50% reduction at a dosage of 1 mg/kg and over 95% reduction at dosages of 3 or 10 mg/kg over a two-week period. This is noteworthy because paw volume measurements commence on day 0 of treatment in animals already exhibiting considerable disease symptoms, enabling observations of over 100% inhibition in cases where animals demonstrate significant swelling reductions. Furthermore, at a daily dose of 0.7 mg, Baricitinib-treated mice show markedly decreased inflammation, as evidenced by H&E staining, alongside reduced CD8 infiltration, and lowered MHC class I and II expression relative to vehicle-control treated mice. Additionally, the presence of CD8+NKG2D+ cells, pivotal in the progression of both murine and human alopecia areata (AA), is substantially reduced in Baricitinib-treated mice when compared to those treated with the vehicle control.
• In Vitro:
  Baricitinib (INCB028050) effectively inhibits JAK signaling and function in various cell-based assays, showcasing its potent anti-inflammatory properties. In Peripheral Blood Mononuclear Cells (PBMCs), it impedes IL-6-induced phosphorylation of STAT3 (pSTAT3) and reduces MCP-1 chemokine production, with half-maximal inhibitory concentrations (IC50) of 44 nM and 40 nM, respectively. Further, in naive T-cells, Baricitinib blocks pSTAT3 activation by IL-23 with an IC50 of 20 nM, crucially preventing the release of inflammatory cytokines IL-17 and IL-22 from Th17 cells, at an IC50 of 50 nM. Unlike Baricitinib, the structurally similar JAK1/2 inhibitors INCB027753 and INCB029843 show no significant activity in these assays even at concentrations up to 10 μM.
• Cell Research:
  Baricitinib(INCB 028050) is dissolved in stock solutions, and then diluted with appropriate media before use. 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.

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Baricitinib, Baricitinib Phosphate, INCB-028050, INCB028050 Phosphate, INCB-028050 phosphate, INCB 028050, INCB 028050 Phosphate, JAK3, JAK2, JAK1, JAK, LY-3009104, LY3009104 Phosphate, LY-3009104 phosphate, LY 3009104, LY 3009104 Phosphate, Tyk2, Tyrosine Kinases, TyrosineKinases

Compound Identifiers

PubChem CID

44231848