{"doi":"10.1002/cmdc.202000465","title":"Purinergic Signaling: Impact of GPCR Structures on Rational Drug Design","abstract":"Abstract The purinergic signaling system includes membrane‐bound receptors for extracellular purines and pyrimidines, and enzymes/transporters that regulate receptor activation by endogenous agonists. Receptors include: adenosine (A 1 , A 2A , A 2B, and A 3 ) and P2Y (P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 , P2Y 12 , P2Y 13 , and P2Y 14 ) receptors (all GPCRs), as well as P2X receptors (ion channels). Receptor activation, especially accompanying physiological stress or damage, creates a temporal sequence of signaling to counteract this stress and either mobilize (P2Rs) or suppress (ARs) immune responses. Thus, modulation of this large signaling family has broad potential for treating chronic diseases. Experimentally determined structures represent each of the three receptor families. We focus on selective purinergic agonists (A 1 , A 3 ), antagonists (A 3 , P2Y 14 ), and allosteric modulators (P2Y 1 , A 3 ). Examples of applying structure‐based design, including the rational modification of known ligands, are presented for antithrombotic P2Y 1 R antagonists and anti‐inflammatory P2Y 14 R antagonists and A 3 AR agonists. A 3 AR agonists are a potential, nonaddictive treatment for chronic neuropathic pain.","journal":"ChemMedChem","year":2020,"id":75096,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":233845,"name":"Kenneth A. Jacobson","orcid":"0000-0001-8104-1493","position":1,"is_corresponding":false},{"id":392354,"name":"Veronica Salmaso","orcid":"0000-0001-5305-8351","position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":null,"created_at":"2026-07-18T21:46:33.313355Z","pmid":"32803849","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}