{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hernandez-Olmos V"],"funding":["Ontario Institute for Cancer Research","European Federation of Pharmaceutical Industries and Associations","Kungliga Tekniska H?gskolan","Deutsche Forschungsgemeinschaft","Landes-Offensive zur Entwicklung Wissenschaftlich-?konomischer Exzellenz","Horizon 2020 Framework Programme","McGill University","Fraunhofer Leistungszentrum Innovative Therapeutics","Diamond Light Source"],"pagination":["10567-10588"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11249017"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["67(13)"],"pubmed_abstract":["G protein-coupled receptor G2A was postulated to be a promising target for the development of new therapeutics in neuropathic pain, acute myeloid leukemia, and inflammation. However, there is still a lack of potent, selective, and drug-like G2A agonists to be used as a chemical tool or as the starting matter for the development of drugs. In this work, we present the discovery and structure-activity relationship elucidation of a new potent and selective G2A agonist scaffold. Systematic optimization resulted in (3-(pyridin-3-ylmethoxy)benzoyl)-<i>d</i>-phenylalanine (T-10418) exhibiting higher potency than the reference and natural ligand 9-HODE and high selectivity among G protein-coupled receptors. With its favorable activity, a clean selectivity profile, excellent solubility, and high met"],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Development of a Potent and Selective G2A (GPR132) Agonist."],"pmcid":["PMC11249017"],"funding_grant_id":["875510","SFB1039 - TPA09","PR1405/8-1","SFB1039 - TPA07","PR1405/4-1","SFB1039 - TPA02","SFB1052 - TP C08"],"pubmed_authors":["Zaliani A","Kaiser A","Ivanov VV","Gribbon P","Mathes M","Schermeng T","Beck-Sickinger AG","Moroz YS","Schmachtel T","Haydo AS","Marinescu B","Wolf M","Alnouri MW","Offermanns S","Nevermann S","Proschak E","Hernandez-Olmos V","Heering J","Rieger MA","Steinhilber D","Ehrler JHM","Hofner G","Merk D","Sisignano M","Schubert-Zsilavecz M"],"additional_accession":[]},"is_claimable":false,"name":"Development of a Potent and Selective G2A (GPR132) Agonist.","description":"G protein-coupled receptor G2A was postulated to be a promising target for the development of new therapeutics in neuropathic pain, acute myeloid leukemia, and inflammation. However, there is still a lack of potent, selective, and drug-like G2A agonists to be used as a chemical tool or as the starting matter for the development of drugs. In this work, we present the discovery and structure-activity relationship elucidation of a new potent and selective G2A agonist scaffold. Systematic optimization resulted in (3-(pyridin-3-ylmethoxy)benzoyl)-<i>d</i>-phenylalanine (T-10418) exhibiting higher potency than the reference and natural ligand 9-HODE and high selectivity among G protein-coupled receptors. With its favorable activity, a clean selectivity profile, excellent solubility, and high met","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2026-06-01T13:54:52.742Z","creation":"2026-04-08T13:01:45.29Z"},"accession":"S-EPMC11249017","cross_references":{"pubmed":["38917049"],"doi":["10.1021/acs.jmedchem.3c02164"]}}