{"doi":"10.1016/j.peptides.2019.170139","title":"Apelin-36-[L28A] and Apelin-36-[L28C(30kDa-PEG)] peptides that improve diet induced obesity are G protein biased ligands at the apelin receptor","abstract":null,"journal":"Peptides","year":2019,"id":634273,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1644938,"name":"Rhoda E. Kuc","orcid":null,"position":1,"is_corresponding":false},{"id":1644939,"name":"Thomas L. Williams","orcid":null,"position":2,"is_corresponding":false},{"id":1644940,"name":"Maria Bednarek","orcid":null,"position":3,"is_corresponding":false},{"id":1644941,"name":"Philip Ambery","orcid":null,"position":4,"is_corresponding":false},{"id":238141,"name":"Lutz Jermutus","orcid":"0000-0001-7660-8467","position":5,"is_corresponding":false},{"id":120927,"name":"Janet J. Maguire","orcid":"0000-0002-9254-7040","position":6,"is_corresponding":false},{"id":120926,"name":"Anthony P. Davenport","orcid":"0000-0002-2096-3117","position":7,"is_corresponding":false},{"id":1451584,"name":"Duuamene Nyimanu","orcid":"0000-0002-6212-9518","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Apelin-36-[L28A] and Apelin-36-[L28C(30kDa-PEG)] peptides that improve diet induced obesity are G protein biased ligands at the apelin receptor","abstract":"BACKGROUND: Apelin signalling pathways have important cardiovascular and metabolic functions. Recently, apelin-36-[L28A] and apelin-36-[L28C(30kDa-PEG)], were reported to function independent of the apelin receptor in vivo to produce beneficial metabolic effects without modulating blood pressure. We aimed to show that these peptides bound to the apelin receptor and to further characterise their pharmacology in vitro at the human apelin receptor. METHODS: I]apelin-13 (0.1 nM), and/or increasing concentrations of apelin-36, apelin-36-[L28A] and apelin-36-[L28C(30kDa-PEG)] (50pM-100μM). Apelin-36 and its analogues apelin-36-[F36A], apelin-36-[L28A], apelin-36-[L28C(30kDa-PEG)], apelin-36-[A28 A13] and [40kDa-PEG]-apelin-36 were tested in forskolin-induced cAMP inhibition and β-arrestin assays in CHO-K1 cells heterologously expressing the human apelin receptor. Bias signaling was quantified using the operational model for bias. RESULTS: I]apelin-13 with nanomolar affinities. Apelin-36-[L28A] and apelin-36-[L28C(30kDa-PEG)] inhibited forskolin-induced cAMP release, with nanomolar potencies but they were less potent compared to apelin-36 at recruiting β-arrestin. Bias analysis suggested that these peptides were G protein biased. Additionally, [40kDa-PEG]-apelin-36 and apelin-36-[F36A] retained nanomolar potencies in both cAMP and β-arrestin assays whilst apelin-36-[A13 A28] exhibited a similar profile to apelin-36-[L28C(30kDa-PEG)] in the β-arrestin assay but was more potent in the cAMP assay. CONCLUSIONS: Apelin-36-[L28A] and apelin-36-[L28C(30kDa-PEG)] are G protein biased ligands of the apelin receptor, suggesting that the apelin receptor is an important therapeutic target in metabolic diseases.","is_dataset_classified":null,"base_score":2.833213344056216,"endowment":2.833213344056216,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31472173","pmcid":"PMC6838674","openalex_id":"https://openalex.org/W2970846649","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"WT107715/Z/15/Z ","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_PC_12012","title":null},{"funder_name":"Wellcome Trust","grant_id":"203814","title":"University of Cambridge - Metabolic and Cardiovascular Disease"},{"funder_name":"Wellcome Trust","grant_id":"107715","title":"Identification of 'hit to lead' small molecule biased' apelin receptor agonists for treating pulmonary arterial hypertension (PAH) using HTS and molecular modelling."},{"funder_name":"Wellcome Trust","grant_id":"","title":null}],"total_grants":5,"fwci":1.6039,"citation_percentile":0.81885893,"influential_citations":0,"citation_trend":[{"year":2018,"count":1},{"year":2019,"count":2},{"year":2020,"count":1},{"year":2021,"count":7},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://www.sciencedirect.com/science/article/pii/S0196978119301172/pdf","host_type":"journal"},{"url":"https://www.sciencedirect.com/science/article/pii/S0196978119301172/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0196978119301172?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0196978119301172?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.peptides.2019.170139","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31472173","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6838674","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6838674","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6838674?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.17863/cam.43295","host_type":""},{"url":"http://dx.doi.org/10.1016/j.peptides.2019.170139","host_type":""},{"url":"https://dx.doi.org/10.1016/j.peptides.2019.170139","host_type":""},{"url":"https://doi.org/10.17863/cam.43295","host_type":""},{"url":"https://www.repository.cam.ac.uk/handle/1810/296250","host_type":""}],"fields_of_study":["Apelin-related biomedical research","Cardiovascular, Neuropeptides, and Oxidative Stress Research","GDF15 and Related Biomarkers","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["beta-Arrestins","Apelin","Apelin Receptors","Cyclic AMP","Adult","Animals","Binding, Competitive","Cricetulus","Female","Colforsin","Heart Ventricles","Humans","Ligands","Male","Middle Aged","Peptides","Protein Binding","CHO Cells","Rats, Sprague-Dawley","Complex Mixtures","Rats"],"keywords":["Apelin","Internal medicine","Receptor","Endocrinology","Forskolin","Chemistry","Biology","Medicine","Cardiovascular disease","Human heart","Metabolic Disease","Gpcr","Receptor Affinity","Biased Ligands","Apelin Receptor","Adult","Male","Heart Ventricles","CHO Cells","Complex Mixtures","Ligands","Binding, Competitive","Article","Rats, Sprague-Dawley","Cricetulus","Cyclic AMP","Animals","Humans","beta-Arrestins","Apelin Receptors","Colforsin","Middle Aged","Rats","Female","Peptides","Protein Binding"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T13:25:04.470243Z","pmid":null,"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":[]}