molecules of the month

Preclinical validation for IRAK4 inhibitors for dermatology from activity in human biopsies. Interleukin-1 receptor-associated kinase (IRAK4) is downstream of toll-like receptors (TLRs), which are established mediators of inflammation. Like many immune-signaling nodes (JAK, BTK), this has been of interest for potential treatment of immunological diseases and blood cancers with immune-cell lineages. Paralleling the development of JAK inhibitors, IRAK4 biology was preclinically validated for RA and SLE initially, and now Galapagos is disclosing preclinical validation for dermatology, the ATP-competitive clinical candidate, GLPG2534. Particularly notable here is that IRAK4 inhibition with Galapagos’ compound ameliorated pathogenic molecular signatures in biopsies of diseased human tissue. IRAK4, the “JAK” or “BTK” of innate immunity? Given the massive success of molecules targeting T-cell receptor signaling mediators…