GLPG2534 is an orally active, selective and potent IRAK4 inhibitor with anti-inflammatory activity. GLPG2534 inhibits human and mouse IRAK4 and could be used to study psoriasis and atopic dermatitis.

IL-1β:55 nM, IRAK1:179 nM, IRAK4 (human):6.4 nM, mIRAK4:3.5 nM

GLPG2534 inhibits IL-6 release driven by IL-1β with an IC50 of 55 nM[1]. It also inhibits TNF-α-driven IL-6 release, with an IC50 of 6.6 μM[1]. When applied at concentrations ranging from 0.1 to 10 μM for 16 hours, GLPG2534 inhibits the expression of S100A7, DEFB4A, CXCL8, and TNF in ciliated epithelial cells stimulated with ciliogenesis-promoting factors[1].

GLPG2534, administered orally at doses ranging from 0.3 to 10 mg/kg, inhibits CL097-driven TNF-α release in mouse blood[1]. Furthermore, oral administration of GLPG2534 at doses of 10 and 30 mg/kg, twice daily, alleviates inflammation in a psoriasis-like mouse model[1]. Additionally, GLPG2534, at doses of 3-30 mg/kg, orally administered twice daily for 5 days, mitigates the development of IL-33 and MC903-induced atopic dermatitis-like skin inflammation in mice[1].