GLPG2938 is sphingosine-1-phosphate receptor 2 (S1P2) antagonist.1 It inhibits S1P-induced calcium flux in CHO cells overexpressing human S1P2 (IC50 = 8.8 nM). GLPG2938 inhibits S1P-induced IL-8 release in HFL1 cells (IC50 = 0.6 nM) and S1P-induced contraction of human lung fibroblasts. In vivo, GLPG2938 (3, 10, and 30 mg/kg) prevents epithelial damage and pulmonary fibrosis, structural distortion, and inflammation in a mouse model of bleomycin-induced pulmonary fibrosis.
1.Mammoliti, O., Palisse, A., Joannesse, C., et al.Discovery of the S1P2 antagonist GLPG2938 (1-[2-ethoxy-6-(trifluoromethyl)-4-pyridyl]-3-[[5-methyl-6-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]pyridazin-3-yl]methyl]urea), a preclinical candidate for the treatment of idiopathic pulmonary fibrosisJ. Med. Chem.64(9)6037-6058(2021)