GLPG3312 is a potent and selective pan-SIK inhibitor with IC50 of 2.0/0.7/0.6 nM for SIK1/SIK2/SIK3, respectively.
GLPG3312 displays high selectivity against a panel of 380 kinases, RIPK2 is the most potent off-target with IC50 of 19.7 nM, which is 10-fold less potent than that on SIK1 and 30-fold less potent than those on SIK2 and SIK3.
GLPG3312 dose-dependently inhibits TNFα release in vitro cell assays using primary human monocytes and monocyte-derived macrophages (MdM) stimulated with LPS, with IC50 of 17 nM and 34 nM, respectively, also enhances the release of IL-10 at higher concentrations.
GLPG3312 displays both anti-inflammatory and immunoregulatory activities in vitro, inhibits the production of TNFα and increased the release of IL-10 in mice stimulated with LPS.
