{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang P"],"funding":["NIDA NIH HHS","University of Texas Medical Branch","Pharmaceutical Research and Manufacturers of America Foundation","National Institute on Drug Abuse"],"pagination":["13951-13972"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8428802"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["63(22)"],"pubmed_abstract":["The G protein-coupled receptor 52 (GPR52) is an orphan receptor that is selectively expressed in the striatum and regulates various brain functions through activation of cAMP-dependent pathways. GPR52 has been identified as a promising therapeutic target for central nervous system disorders including schizophrenia and substance use disorders. Here, a series of novel GPR52 agonists were designed, synthesized, and evaluated based on compound <b>4</b>. Several potent and efficacious GPR52 agonists (<b>12c</b>, <b>23a</b>, <b>23d</b>, <b>23e</b>, <b>23f</b>, and <b>23h</b>) were identified with nanomolar range potency based on a systematic structure-activity relationship exploration. Further studies of <b>12c</b> indicate enhanced efficacy, excellent target selectivity, and pharmacokinetic properties including good brain permeability. <i>In vivo</i> proof-of-concept investigations revealed that <b>12c</b> displayed antipsychotic-like activity by significantly inhibiting amphetamine-induced hyperlocomotor behavior in mice. Collectively, our findings have resulted in an efficacious, brain-penetrant GPR52 agonist as a valuable pharmacological tool for investigating the physiological and therapeutic potential of GPR52 activation."],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Discovery of Potent and Brain-Penetrant GPR52 Agonist that Suppresses Psychostimulant Behavior."],"pmcid":["PMC8428802"],"funding_grant_id":["U18 DA052543","T32 DA007287"],"pubmed_authors":["Wang P","Cunningham KA","Allen JA","Murphy RE","Chen H","Stutz SJ","Felsing DE","Zhou J"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of Potent and Brain-Penetrant GPR52 Agonist that Suppresses Psychostimulant Behavior.","description":"The G protein-coupled receptor 52 (GPR52) is an orphan receptor that is selectively expressed in the striatum and regulates various brain functions through activation of cAMP-dependent pathways. GPR52 has been identified as a promising therapeutic target for central nervous system disorders including schizophrenia and substance use disorders. Here, a series of novel GPR52 agonists were designed, synthesized, and evaluated based on compound <b>4</b>. Several potent and efficacious GPR52 agonists (<b>12c</b>, <b>23a</b>, <b>23d</b>, <b>23e</b>, <b>23f</b>, and <b>23h</b>) were identified with nanomolar range potency based on a systematic structure-activity relationship exploration. Further studies of <b>12c</b> indicate enhanced efficacy, excellent target selectivity, and pharmacokinetic properties including good brain permeability. <i>In vivo</i> proof-of-concept investigations revealed that <b>12c</b> displayed antipsychotic-like activity by significantly inhibiting amphetamine-induced hyperlocomotor behavior in mice. Collectively, our findings have resulted in an efficacious, brain-penetrant GPR52 agonist as a valuable pharmacological tool for investigating the physiological and therapeutic potential of GPR52 activation.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Nov","modification":"2024-11-12T17:25:25.595Z","creation":"2022-02-11T10:57:59.475Z"},"accession":"S-EPMC8428802","cross_references":{"pubmed":["33198466"],"doi":["10.1021/acs.jmedchem.0c01498"]}}