Baricitinib phosphate [1187595-84-1]

Direct and indirect inhibition of the JAKs has demonstrated rapid and sustained improvement in clinical measures of disease. Baricitinib phosphate (INCB 028050) is a selective JAK1 and JAK2 inhibitor.

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].

In vivo: Significant efficacy was achieved in the rat adjuvant arthritis model with doses of Baricitinib phosphate providing partial and/or periodic inhibition of JAK1/JAK2 and no inhibition of JAK3. Baricitinib phosphate was also effective in multiple murine models of arthritis, with no evidence of suppression of humoral immunity or adverse hematologic effects [2].

Clinical trial: Several clinical trials have been conducted to investigated the PK, efficacy and DDI of Baricitinib phosphate in healthy people as well as in participants With Rheumatoid Arthritis.

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.