GPR35: from enigma to therapeutic target

The orphan G-protein-coupled receptor 35 (GPR35), although poorly characterised, is attracting considerable interest as a therapeutic target. Marked differences in pharmacology between human and rodent orthologues of the receptor and a dearth of antagonists with affinity for mouse and rat GPR35 have previously restricted the use of preclinical disease models. The development of improved ligands, novel transgenic knock-in mouse lines, and detailed analysis of the disease relevance of single-nucleotide polymorphisms (SNPs) have greatly enhanced understanding of the key roles of GPR35 and have stimulated efforts towards disease-targeted proof-of-concept studies. In this opinion article, new information on the biology of the receptor is considered, whilst insight into how GPR35 is currently being assessed for therapeutic utility - in areas ranging from inflammatory bowel diseases to nonalcoholic steatohepatitis and various cancers - is also provided.

Automated summary

Despite being poorly characterised, orphan G-protein-coupled receptor 35 (GPR35) has attracted significant interest as a therapeutic target. Differences in pharmacology between human and rodent orthologues of the receptor have restricted preclinical disease models, but recent developments in ligands, transgenic mouse models, and analysis of single-nucleotide polymorphisms (SNPs) have improved understanding and stimulated disease-targeted proof-of-concept studies. This opinion article provides new insights into the biology of GPR35 and discusses its therapeutic potential in various diseases.