Studying inflammatory diseases with a chemical probe for IRAK4
The Ser/Thr kinase IRAK4 (interleukin-1 receptor-associated kinase 4) is involved in signaling innate and adaptive immune responses. As its kinase activity is essential for TLR-induced B cell differentiation and Type I interferon production, IRAK4 plays a critical role in multiple autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, gout, and others.
The evaluation of numerous available IRAK4 small-molecule inhibitors in combination with structure-based drug design resulted in the chemical probe GNE-2256 with optimized properties. The probe is highly selective within the kinome and its application leads to a reduction of multiple pro-inflammatory cytokines in vivo.
The chemical probe GNE-2256 together with its negative control GNE-6689 is ideally suited to explore the role of IRAK4 in diverse inflammatory or auto-immune diseases.
Left: Binding mode of GNE-2256 in IRAK4 (PDB 6UYA). Right: Selectivity profile of GNE-2256 within kinome.
For more information about the GNE-2256 chemical probe visit the SGC Donated Chemical Probes:
Request the chemical probe GNE-2256 and its negative control GNE-6689 from the SGC Donated Chemical Probes.