Baricitinib phosphate salt is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays.

Uses

Baricitinib phosphate salt is useful for the treatment of inflammatory diseases and autoimmune diseases such as rheumatoid arthritis, psoriasis , diabetes, kidney disease, dermatitis and lupus erythematosus, and especially for the treatment of rheumatoid arthritis.

Mechanism of action

Baricitinib phosphate salt is a JAK kinase inhibitor that inhibits the JAK-STAT signaling pathway in cells in vivo. Since the JAK-STAT signaling pathway is associated with immune responses and immune regulation in the human body, immune cells will use this route of transmission to form an inflammatory response. Therefore, when the JAK-STAT signaling pathway is inhibited, immune-related diseases can be suppressed, and the JAK-STAT signaling pathway in leukemia cells is always activated, and can be controlled when JAK inhibitors are used to suppress signal transmission. leukemia. JAK has four types of JAK1, JAK2, JAK3, and JAK4, while Baricitinib phosphate is a JAK1 and JAK2 inhibitor.

Crystal forms

At present, the original phosphate salt of Barrickinib is manufactured by Incyte Pharmaceuticals, and its preparation method has been disclosed in PCT Patent Publication No. WO 2009114512A1. The PCT Patent Publication No. WO 2016141892A1 has disclosed three crystal forms of Barretinib phosphate salt, which are Form A, Form B and Form C, respectively; Chinese Patent Publication No. CN 105601635A has disclosed four types of Barrickinib ( Baricitinib) is a crystalline form of crystalline form A, crystalline form H, crystalline form I and crystalline form X. The crystalline form X is the original barretinib phosphate crystal form manufactured by Ince Pharmaceuticals.

In vitro study

In vitro: Baricitinib phosphate is a selective orally bioavailable JAK1/JAK2 inhibitor with nanomolar potency against JAK1 (5.9 nM) and JAK2 (5.7 nM) and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. INCB028050 inhibits intracellular signaling of multiple proinflammatory cytokines including IL-6 and IL-23 at concentrations, 50 nM [1].

Reference

[1] Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, Favata MF, Wen X, Shi J, McGee R, Haley PJ, Shepard S, Rodgers JD, Yeleswaram S, Hollis G, Newton RC, Metcalf B, Friedman SM, Vaddi K.Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol. 2010;184(9):5298-307.