Baricitinib

Baricitinib, also known as INCB028050 or LY3009104, is a selective orally bioavailable JAK1/JAK2 inhibitor with nanomolar potency against JAK1 (5.9 nM) and JAK2 (5.7 nM). INCB028050 inhibits intracellular signaling of multiple proinflammatory cytokines including IL-6 and IL-23 at concentrations <50 nM. INCB028050 was also effective in multiple murine models of arthritis, with no evidence of suppression of humoral immunity or adverse hematologic effects. Baricitinib was approved for the treatment of rheumatoid arthritis (RA) in the United States.

Product information

CAS Number: 1187594-09-7

Molecular Weight: 371.42

Formula: C16H17N7O2S

Synonym:

INCB-028050

LY-3009104

Olumiant

INCB028050

INCB 028050

LY3009104

LY 3009104

Baricitinib

Chemical Name: 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(ethylsulfonyl)azetidin-3-yl)acetonitrile

Smiles: CCS(=O)(=O)N1CC(C1)(CC#N)N1C=C(C=N1)C1N=CN=C2NC=CC=12

InChiKey: XUZMWHLSFXCVMG-UHFFFAOYSA-N

InChi: InChI=1S/C16H17N7O2S/c1-2-26(24,25)22-9-16(10-22,4-5-17)23-8-12(7-21-23)14-13-3-6-18-15(13)20-11-19-14/h3,6-8,11H,2,4,9-10H2,1H3,(H,18,19,20)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

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[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.

References:

1. Krutzke S, Rietschel C, Horneff G. Baricitinib in therapy of COPA syndrome in a 15-year-old girl. Eur J Rheumatol. 2019 Aug 20:1-4. doi: 10.5152/eurjrheum.2019.18177. [Epub ahead of print] Review. PubMed PMID: 31449490.
2. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548012/ PubMed PMID: 31643344.
3. Clinical Review Report: Baricitinib (Olumiant): (Eli Lilly Canada Inc.): Indication: For use in combination with methotrexate (MTX) for the treatment of adult patients with moderate to severe rheumatoid arthritis who have responded inadequately to one or more disease-modifying antirheumatic drugs (DMARDs). Baricitinib may also be used as monotherapy in cases of intolerance to MTX [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Sep. Available from http://www.ncbi.nlm.nih.gov/books/NBK549711/ PubMed PMID: 31742964.

Products are for research use only. Not for human use.