别名 interleukin 1 receptor associated kinase 4、Interleukin-1 receptor-associated kinase 4、IRAK-4 + [3] |
简介 Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. |
靶点 |
作用机制 IRAK4抑制剂 |
在研机构 |
原研机构 |
非在研适应症- |
最高研发阶段临床2期 |
首次获批国家/地区- |
首次获批日期1800-01-20 |
靶点 |
作用机制 IRAK4抑制剂 |
在研适应症 |
最高研发阶段临床2期 |
首次获批国家/地区- |
首次获批日期1800-01-20 |
开始日期2025-11-16 |
申办/合作机构 |
开始日期2025-04-28 |
申办/合作机构 |
开始日期2025-04-17 |