GLPG2534 is a potent, selective and orally active IRAK4 inhibitor with IC50 values of 6.4 nM and 3.5 nM for human and mouse IRAK4. In vitro, IRAK4 inhibition resulted in substantial inhibition of TLR and IL-1 responses in dendritic cells, keratinocytes, granulocytes, and T cells but only weakly affected dermal fibroblast responses. Furthermore, disease activity in murine models of skin inflammation (IL-23–, IL-33–, imiquimod-, and MC903-induced) was markedly dampened by IRAK4 inhibition. Last, inhibiting IRAK4 reversed pathogenic molecular signatures in human lesional psoriasis and atopic dermatitis biopsies.

KEYWORDS: GLPG2534 | IRAK4 inhibitor | GLPG 2534 | GLPG-2534 | CAS [2095615-97-5] | Interleukin | IRAK | Inhibitor | Enzymes | Innate immunity | Inflammatory skin disease | Psoriasis | Atopic dermatitis