Orphan Receptor GPR88 as an Emerging Neurotherapeutic Target

Na Ye, Bang Li, Qi Mao, Eric A. Wold, Sheng Tian, John Allen, Jia Zhou

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations


Although G protein-coupled receptors (GPCRs) are recognized as pivotal drug targets involved in multiple physiological and pathological processes, the majority of GPCRs including orphan GPCRs (oGPCRs) are unexploited. GPR88, a brain-specific oGPCR with particularly robust expression in the striatum, regulates diverse brain and behavioral functions, including cognition, mood, movement control, and reward-based learning, and is thus emerging as a novel drug target for central nervous system disorders including schizophrenia, Parkinson's disease, anxiety, and addiction. Nevertheless, no effective GPR88 synthetic ligands have yet entered into clinical trials, and GPR88 endogenous ligands remain unknown. Despite the recent discovery and early stage study of several GPR88 agonists, such as 2-PCCA, RTI-13951-33, and phenylglycinol derivatives, further research into GPR88 pharmacology, medicinal chemistry, and chemical biology is urgently needed to yield structurally diversified GPR88-specific ligands. Drug-like pharmacological tool function and relevant signaling elucidation will also accelerate the evaluation of this receptor as a viable neurotherapeutic target.

Original languageEnglish (US)
Article number10.1021/acschemneuro.8b00572
Pages (from-to)190-200
Number of pages11
JournalACS Chemical Neuroscience
Issue number1
StatePublished - Jan 16 2019


  • CNS disorders
  • GPR88
  • Orphan G protein-coupled receptors (oGPCRs)
  • agonists
  • drug discovery
  • neurotherapeutics
  • striatum

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology


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