2. Academic Validation
  3. Discovery and optimization of a potent and selective indazolamine series of IRAK4 inhibitors

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

  • Bioorg Med Chem Lett. 2021 Jan 1;31:127686. doi: 10.1016/j.bmcl.2020.127686.
Wenqiang Zhai 1,  Yongping Lu 1,  Yabo Zhu 1,  Mengguang Zhou 1,  Cheng Ye 1,  Zheng-Zheng Shi 1,  Wenjian Qian 2,  Taishan Hu 1,  Lei Chen 1
Affiliations

Affiliations

  • 1 Zhejiang Hisun Pharmaceutical Co. Ltd., China, 46 Waisha Rd., Taizhou 318099, China.
  • 2 Zhejiang Hisun Pharmaceutical Co. Ltd., China, 46 Waisha Rd., Taizhou 318099, China. Electronic address: [email protected].
PMID: 33242574 DOI: 10.1016/j.bmcl.2020.127686
Abstract

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 TNFα production and collagen-induced arthritis.

Keywords

Collagen-induced arthritis; IRAK4; Indazole; Inflammation; TNFα.

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