Upadacitinib

Upadacitinib (ABT-494) is a potent and selective JAK1 inhibitor with celluar IC50 of 8 nM, biochemical IC50 of 40 nM; displays 74-fold and 50-fold selectivity over JAK2 and JAK3, respectively; a second-generation JAK inhibitor in development for rheumatoid arthritis.Rheumatoid Arthritis Phase 3 Clinical(In Vitro):In biochemical assays, Upadacitinib is 74-fold more selective for JAK-1 than for JAK-2 (which is involved in erythropoiesis) and 58-fold more selective for JAK-1 than for JAK-3 (which is involved in immunosurveillance). The enhanced selectivity of Upadacitinib for JAK-1 over JAK-2 and JAK-3 may offer an improved benefit–risk profile in patients with RA range.(In Vivo):Upadacitinib (0.1-10 mg/kg; oral gavage; twice a day for 10 days) demonstrates efficacy in rat arthritis models.