Description
HS271 is a highly potent, orally active and selective IRAK4 inhibitor, with an IC 50 of 7.2 µM. HS271 exhibits superior enzymatic and cellular activities, as well as excellent pharmacokinetic propertiesIn VivoHS271 (15-150 mg/kg) displays robust in vivo antiinflammatory efficacy as evaluated in rat models of LPS induced TNFα production collageninduced arthritis. HS271 exhibits a t 1/2 of 3.3 h and C max of 2107 ng/mL. HS271 is stable in liver microsome assays across other species, including rat, mouse, monkey, and human. HS271 exhibits oral bioavailability of 67.3%, 58.2%, 14.4&% and 49% in mouse, rat, dog and monkey, respectively. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: A rat model of collagen induced arthritis (CIA). Dosage: 15, 50, 150 mg/kg. Administration: PO, once daily. Result: Led to a significant reduction in paw swelling as compared to vehicle control, with a minimum effective dose at 15 mg/kg QD. Notably, at 150 mg/kg QD, HS271 eliminated the paw swelling.IC50& Target:IRAK4 7.2 µM (IC 50 )