A Comprehensive Review on IRAK-4 Inhibitors

Interleukin-1 receptor-associated kinases (IRAKs) are key component in the signal transduction utilized by interleukin-1 receptor (IL-1R), interleukin-18 receptor (IL-18R), and Toll-like receptors (TLRs). It plays a pivotal role in alleviating chronic inflammatory and autoimmune disorders. IRAK-4 is also known as “master IRAK” due its role in IL-1R/TLR signaling. Various potent series with IRAK4 inhibitory activity have been reported., including Thiazole and Pyridine Amides, Aminobenzimidazoles, Imidazo[1,2-a]pyridines and Imidazo[1,2-b]pyridazine and Indazole inhibitors. Here, we have presented a comprehensive review on IRAK-4 mechanism of action, SAR activity of known IRAK-4 inhibitors.