Upadacitinib (ABT-494) is a selectiveJAK1inhibitor which demonstrates activity against JAK1 (0.045 μM) and JAK2 (0.109 μM), with > 40 fold selectivity over JAK3 (2.1 μM) and 100 fold selectivity over TYK2 (4.7 μM) as compared to JAK1. In vitro
Upadacitinib is most potent on JAK1compared to other family members (JAK1\u2009>\u2009JAK2\u2009>\u2009JAK3\u2009>\u2009TYK2). Upadacitinib demonstrates selectivity across a broad panel of 70+ kinases, with only Rock1 and Rock2 demonstrating IC50 values below 1 μM. Consistent with the Ba/F3 cellular data, upadacitinib potently inhibits the JAK1 dependent cytokines IL-6, OSM, IL-2, and IFNγ, as measured by inhibition of STAT phosphorylation.
In vivo
Upadacitinib inhibits disease pathology in rat adjuvant induced arthritis. It is a non-sensitive substrate for cytochrome P450, approximately 20% is eliminated, unchanged, in urine. Cell Data
