GS-9901

GS-9901 is a highly selective and orally active PI3Kδ inhibitor, with an IC50 of 1 nM. Has potential to treat rheumatoid arthritis[1].

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

Research Areas >> Inflammation/Immunology

PI3Kδ:1 nM (IC50)

GS-9901 (0.3/1/3 mg/kg, orally, twice daily for 7 days) demonstrates efficacy in a rat model of arthritis and is predicted to be suitable for q.d. dosing in humans[1]. Animal Model: Female Lewis rats with established collagen-induced arthritis (CIA)[1]. Dosage: 0.3 mg/kg, 1 mg/kg, and 3 mg/kg. Administration: Orally, twice-daily for 7 days starting on the 10th day after the second collagen immunization. Result: Demonstrated significant reduction in ankle swelling in rats treated with 0.3 mg/kg 35 (31% reduction), 1 mg/kg 35 (67%), and 3 mg/kg 35 (65%). Plasma concentrations measured on day 7 (12 h after last dose) were consistent with maintaining approximately 60%, 80%, and >90% inhibition of PI3Kδ at 0.3, 1.0, and 3 mg/kg doses, respectively, at trough levels.

[1]. Patel L, et al. Discovery of Orally Efficacious Phosphoinositide 3-Kinase δ Inhibitors with Improved Metabolic Stability. J Med Chem. 2016 Oct 13;59(19):9228-9242.