CLH536

CLH536 is a novel small molecule antagonist of GPR84, a G protein-coupled receptor primarily expressed in myeloid cells such as neutrophils, monocytes, and macrophages. GPR84 expression is upregulated during acute inflammatory responses and has been implicated in the pathogenesis of inflammatory and fibrotic diseases. CLH536 was discovered by researchers at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences. It suppresses colitis by reducing the polarization and function of pro-inflammatory macrophages through inhibition of GPR84 signaling, which otherwise enhances NLRP3 inflammasome activation in these immune cells. Preclinical studies have shown efficacy in models of ulcerative colitis; additional potential indications include chronic kidney disease (stage V), interstitial nephritis, renal fibrosis, multiple sclerosis, arthritis, and other diseases associated with hyperactivity or overexpression of GPR84[1][2][3][5].