TLRs can recognize a variety of microbial ligands, recruit MyD88, IRAK4 and IRAK1 molecules to form Myddosome complexes while IRAK4 is phosphorylated itself, and subsequently initiate the cascade of downstream events by actiating IRAK1, IKB kinase (IKK), NF-kappa B, eventually induce pro-inflammatory cytokines gene transcription and expression.

IRAK4 is the key node of IL-1 / TLR signaling pathways with the bi-function: structure and activation to initiate the inner immune system or lead to autoimmune diseases under excessive immune reaction.

The Protein Degrader molecules designed by Leadingtac are capable of both powerfully degrading IRAK4 and inhibiting IRAK4 kinase with the strong immunosuppressive effect.

Data showed that the people deficient in IRAK4 is resistant to autoimmune diseases and is totally healthy at the age of >12.