Opportunities and challenges in drug discovery targeting the orphan receptor GPR12

Pingyuan Wang; Ling Lv; Haoran Li; Chang-Yun Wang; Jia Zhou

doi:10.1016/j.drudis.2023.103698

Opportunities and challenges in drug discovery targeting the orphan receptor GPR12

Drug Discov Today. 2023 Sep;28(9):103698. doi: 10.1016/j.drudis.2023.103698. Epub 2023 Jul 6.

Authors

Pingyuan Wang¹, Ling Lv², Haoran Li³, Chang-Yun Wang⁴, Jia Zhou⁵

Affiliations

¹ Key Laboratory of Evolution and Marine Biodiversity Ministry of Education, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China; School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. Electronic address: wangpingyuan@ouc.edu.cn.
² Key Laboratory of Evolution and Marine Biodiversity Ministry of Education, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China; College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.
³ Key Laboratory of Evolution and Marine Biodiversity Ministry of Education, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China; School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
⁴ Key Laboratory of Evolution and Marine Biodiversity Ministry of Education, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China; School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China. Electronic address: changyun@ouc.edu.cn.
⁵ Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: jizhou@utmb.edu.

PMID: 37422169
DOI: 10.1016/j.drudis.2023.103698

Abstract

G-protein-coupled receptor 12 (GPR12) is a brain-specific expression orphan G-protein-coupled receptor (oGPCR) that regulates various physiological processes. It is an emerging therapeutic target for central nervous system (CNS) disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), attention deficit hyperactivity disorder (ADHD), and schizophrenia, as well as other human diseases, such as cancer, obesity, and metabolic disorders. GPR12 remains a less extensively investigated oGPCR, particularly in terms of its biological functions, signaling pathways, and ligand discovery. The discovery of drug-like small-molecule modulators to probe the brain functions of GPR12 or to act as a potential drug candidates, as well as the identification of reliable biomarkers, are vital to elucidate the roles of this receptor in various human diseases and develop novel target-based therapeutics.

Keywords: GPR12; central nervous system disorders; drug discovery; modulators; neurotherapeutics; oGPCR.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Central Nervous System Diseases* / drug therapy
Drug Discovery
Humans
Ligands
Receptors, G-Protein-Coupled* / metabolism
Signal Transduction / physiology

Substances

Receptors, G-Protein-Coupled
Ligands
GPR12 protein, human