JAK1/3-IN-1

JAK1/3-IN-1 (Compound 35) is a selective, orally active JAK1/3 inhibitor with IC₅₀ values of 1.9 nM and 0.9 nM, respectively. JAK1/3-IN-1 significantly reduces the mean arterial blood pressure and significantly increases the heart rate in rabbits. JAK1/3-IN-1 decreases the mean arterial blood pressure in conscious telemetered rats and induces lethal cardiovascular effects^[1]. In Vitro:JAK1/3-IN-1 potently inhibits purified JAK1, JAK3, TYK2, JAK2, Rho kinase 1, and Rho kinase 2, with IC₅₀ values of 1.9 nM, 0.9 nM, 25 nM, 15 nM, 95 nM, and 43 nM, respectively^[1].
JAK1/3-IN-1 inhibits IL-2-induced IFN-γ production in whole blood with an IC₅₀ of 100 nM^[1].
JAK1/3-IN-1 (10 μM) exhibits moderate Caco-2 cell permeability, a long human microsomal half-life, and no PXR activation activity. At a concentration of 10 μM, it shows a 16% inhibition rate on Ca²⁺ channels and a 71% inhibition rate on Na⁺ channels, with moderate cross-species plasma protein binding levels^[1]. In Vivo:JAK1/3-IN-1 exhibits excellent inhibitory activity against JAK1/3-mediated ex vivo processes in a mouse PD model, with an EC₅₀ of 67 nM^[1].
Single administration of JAK1/3-IN-1 (>3 mg/kg) significantly reduces the mean arterial blood pressure and increases the heart rate in rabbits^[1].
JAK1/3-IN-1 (30-200 mg/kg; p.o.; single administration) reduces the mean arterial blood pressure of conscious telemetered rats and induces lethal cardiovascular effects^[1].