JAK3-IN-18 is a selective and orally active dual inhibitor targeting JAK3 and TEC, with IC50 values of 0.5391 nM and 12.40 nM, respectively. It demonstrates remarkable selectivity for AK1, AK2, and TYK2, with selectivity ratios exceeding 10,000-fold. JAK3-IN-18 exhibits exceptional therapeutic efficacy in a mouse model of experimental autoimmune encephalomyelitis and is applicable for multiple sclerosis research.

JAK3:0.5391 nM

JAK3-IN-18 (Compound 8a) has an IC50 value of 177.8 nM for inhibiting p-STAT5 in IL-15 stimulated human whole blood assays when used in concentrations from 1 to 100000 nM for 80 minutes. At 1 μM concentration for 135 minutes, it suppresses over 60% activity in 11 kinases, excluding JAK3 and TEC, out of a panel of 310 kinases. JAK3-IN-18 at 10 μM for up to 60 minutes demonstrates good stability in GSH and possesses favorable drug-like properties.

JAK3-IN-18 (Compound 8a), administered orally at 10-100 mg/kg twice daily for 24 days, demonstrates exceptional therapeutic efficacy in a mouse model of experimental autoimmune encephalomyelitis (EAE), which is used to study multiple sclerosis.