HS271 is a highly potent, orally active and selective IRAK4 inhibitor, with an IC50 of 7.2 μM. HS271 exhibits superior enzymatic and cellular activities, as well as excellent pharmacokinetic properties[1].
HS271 (15-150 mg/kg) displays robust in vivo antiinflammatory efficacy as evaluated in rat models of LPS induced TNFα production collageninduced arthritis[1].HS271 exhibits a t1/2 of 3.3 h and Cmax of 2107 ng/mL[1].HS271 is stable in liver microsome assays across other species, including rat, mouse, monkey, and human[1].HS271 exhibits oral bioavailability of 67.3%, 58.2%, 14.4&% and 49% in mouse, rat, dog and monkey, respectively[1].
[1]. Wenqiang Zhai, et al. Discovery and optimization of a potent and selective indazolamine series of IRAK4 inhibitors. Bioorg Med Chem Lett. 2020 Nov 24;31:127686.