Discovery and optimization of a potent and selective indazolamine series of IRAK4 inhibitors

IRAK4 is a key mediator of innate immunity. There is a high interest in identifying novel IRAK4 inhibitors for the treatment of inflammatory autoimmune diseases. We describe here a highly potent and selective IRAK4 inhibitor (HS271) that exhibited superior enzymatic and cellular activities, as well as excellent pharmacokinetic properties. HS271 displayed robust in vivo anti-inflammatory efficacy as evaluated in rat models of LPS induced TNF alpha production and collagen-induced arthritis.

Automated summary

HS271 is a highly potent and selective IRAK4 inhibitor with superior enzymatic and cellular activities, as well as excellent pharmacokinetic properties. It exhibited robust in vivo anti-inflammatory efficacy in rat models of LPS-induced TNF alpha production and collagen-induced arthritis.