GLPG1205

GLPG1205 is potent, selective and orally active GPR84 (a G-protein-coupled receptor) antagonist with a favorable PK/PD profile. GLPG1205 has anti-inflammatory activity and is used for the treatment of pulmonary fibrosis[1][2].

Research Areas >> Inflammation/Immunology

Signaling Pathways >> GPCR/G Protein >> GPR84

GLPG1205 (0.5 μM) completely inhibits the ZQ16-induced [Ca2+]i response in neutrophils[1]. GLPG1205 (1 μM; for 5 min) completely blocks the ROS-response induced by the GPR84-agonist[1]. GLPG1205 can potently antagonizes ZQ16-induced ROS with an IC50 value of 15 nM in TNF-α primed neutrophils[1].

GLPG1250 (orally adminstation; 30mg/kg; twice daily) for 2 weeks, starts from 7 days post-challenge,greatly reduces the Ashcroft score, in idiopathic pulmonary fibrosis model[3]. GLPG1250 (orally adminstation; 30mg/kg; once daily) starts from 18 weeks post irradition, significantly reduces college deposition in the mouse lung. Additionlly, GLPG1250 inhibits the increase in MnSOD in lung bronchial epithelial cells and parenchymal macrophages, in the irradiation model[3]. GLPG1205 dose dependently decreases disease activity, histological activity, neutrophil influx and colonic MPO content,in a mouse IBD model[4].

[1]. Sundqvist M, et al. Similarities and differences between the responses induced in human phagocytes through activation of the medium chain fatty acid receptor GPR84 and the short chain fatty acid receptor FFA2R. Biochim Biophys Acta Mol Cell Res. 2018 May;1865(5):695-708.

[2]. F. Vanhoutte, et al. Human safety, pharmacokinetics and pharmacodynamics of the GPR84 antagonist GLPG1205, a potential new approach to treat IBD.

[3]. L.Saniere, et al. Characterization of GLPG1205 in Mouse Fibrosis Models: A Potent and Selective Antagonist of GPR84 for Treatment of Idiopathic Pulmonary Fibrosis. American Journal of Respiratory and Critical Care Medicine 2019;199:A1046

[4]. F. Vanhoutte, et al. Human safety, pharmacokinetics and pharmacodynamics