Journal
TRENDS IN PHARMACOLOGICAL SCIENCES
Volume 44, Issue 5, Pages 263-273Publisher
CELL PRESS
DOI: 10.1016/j.tips.2023.03.001
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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.
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.
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