JAK3-IN-9 is a potent and orally active inhibitor of the Janus kinase 3 (JAK3) enzyme, displaying an impressive IC50 value of 1.7 nM. It exhibits high selectivity towards the JAK3 signaling pathway, making it a valuable tool for studying autoimmune diseases. Additionally, JAK3-IN-9 possesses desirable characteristics such as low toxicity and excellent oral bioavailability. It also demonstrates promising anti-arthritis activity, thus enhancing its potential as a therapeutic agent [1].

JAK3:1.7 nM

JAK3-IN-9 (compound 11i) selectively inhibits JAK3 with an IC50 of 1.7 nM [1]. In Cell Viability Assays using PBMCs at 1 μM concentration and 30-minute incubation, it shows preferential inhibition of JAK3 [1].

JAK3-IN-9, referred to as compound 11i, demonstrated selective inhibition of JAK3 cytokine signaling in primary cells when administered orally at dosages of 3, 10, and 30 mg/kg to female Lewis rats once daily for 20 days. Additionally, it exhibited a high area under the curve (AUC) of 2104 μg/ml, increased the half-life to 2.56 hours, and showed favorable oral bioavailability of 48% upon a single intravenous injection at 1 mg/kg in male DBA1j mice aged 8 to 12 weeks. Furthermore, JAK3-IN-9 significantly reduced paw swelling in a dose-dependent manner, with an effective dose (ED50) value of 10 mg/kg, after oral administration once daily for 20 days at a dose of 30 mg/kg. These results, obtained from studies conducted on male DBA1j mice and female Lewis rats, indicate its potential as an anti-arthritis agent in the CIA mice model.