GLPG0974

GLPG0974 is an antagonist of free fatty acid receptor 2 (FFAR2/GPR43; IC₅₀ = 9 nM).¹ It is selective for FFAR2 over FFAR3 at concentrations up to 30 μM and over a panel of 55 receptors, ion channels, and transporters at 10 μM. GLPG0974 inhibits acetate-induced migration of isolated human neutrophils in buffer or plasma (IC₅₀s = 27 and 43 nM, respectively), as well as acetate-induced expression of CD11b activation-specific epitope on neutrophils in isolated human whole blood (IC₅₀ = 438 nM). GLPG0974 also inhibits a human FFAR2-based designer receptor exclusively activated by designer drugs (hFFAR2-DREADD; IC₅₀ = 36.31 nM in a cell-based β-arrestin-2 recruitment assay).² It inhibits glucagon-like peptide 1 (GLP-1) secretion induced by the hFFA2-DREADD ligand sorbic acid in isolated colonic crypts from mice expressing hemagglutinin-tagged hFFAR2-DREADD when used at a concentration of 10 μM.

WARNING This product is not for human or veterinary use.

1. Pizzonero, M., Dupont, S., Babel, M., et al. Discovery and optimization of an azetidine chemical series as a free fatty acid receptor 2 (FFA₂) antagonist: From hit to clinic. J. Med. Chem. 57(23), 10044-10057 (2014).

2. Bolognini, D., Barki, N., Butcher, A.J., et al. Chemogenetics defines receptor-mediated functions of short chain free fatty acids. Nat. Chem. Biol. 15(5), 489-498 (2019).