Baricitinib, Free Base

Soluble in DMSO. Baricitinib, also known as INCB028050, is a janus kinase (JAK) inhibitor. It potently and selectively inhibited JAK1 and JAK2 kinases with IC50 values of 5.9 nM and 5.7 nM, respectively. It inhibited intracellular signaling of multiple proinflammatory cytokines including IL-6 and IL-23, with IC50 values of <50 nM. Baricitinib at doses providing partial and/or periodic inhibition of JAK1/JAK2 significantly improved rheumatoid arthritis as assessed by clinical, histologic and radiographic signs of disease in the rat adjuvant arthritis model. It was also effective in multiple murine models of arthritis. Fridman J.S., et al. 'Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050.' J. Immunol. 184: 5298-5307 (2010). Baricitinib was well tolerated and demonstrated clinically meaningful responses in patients with active rheumatois arthritis. Greenwald M.W., et al. 'A Randomized Dose-Ranging, Placebo-Controlled Study of INCB028050, a Selective JAK1 and JAK2 Inhibitor in Subjects with Active Rheumatoid Arthritis.' http://www.blackwellpublishing.com/acrmeeting/abstract.asp?MeetingID=774&id=90814. Baricitinib reversed alopecia areata in in vivo preclinical studies and in patients. Jabbari A., et al. 'Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.' EBioMedicine. 2: 351-355 (2015).