Decernotinib

Decernotinib is a potent, orally active JAK3 inhibitor, with K_is of 2.5, 11, 13 and 11 nM for JAK3, JAK1, JAK2, and TYK2, respectively. IC50 & Target: Ki: 2.5 (JAK3), 11 (JAK1), 13 (JAK2), 11 nM (TYK)^[1] In Vitro: Decernotinib (VX-509) is a potent JAK3 inhibitor, with K_is of 2.5, 11, 13 and 11 nM for JAK3, JAK1, JAK2, and TYK2, respectively. Decernotinib potently blocks T-cell proliferation with a mean IC₅₀ of 170 ± 101 nM, and inhibits IL-2-stimulated T-cell proliferation (IC₅₀, 140 and 400 nM). VX-509 is also cytotoxic to B-cell in response to CD40L and IL-4 (IC₅₀, 50 nM)^[1]. In Vivo: Decernotinib (VX-509, 10, 25, or 50 mg/kg, p.o.) significantly and dose-dependently inhibits the increases in ankle diameter and paw weight occuring in response to collagen injections in rats. Decernotinib potently alleviates cartilage damage and bone resorption in rats. Decernotinib (10, 25, or 50 mg/kg, p.o., b.i.d.) suppresses ear edema in a mouse model of delayed-type hypersensitivity^[1].