{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:13:03Z","timestamp":1789409583052,"version":"build-2803163510"},"reference-count":32,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL139065"],"award-info":[{"award-number":["R01HL139065"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR082533"],"award-info":[{"award-number":["R01AR082533"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.ejmech.2025.118408","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T08:00:35Z","timestamp":1764403235000},"page":"118408","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Development of activators for SERCA2a for heart failure treatments"],"prefix":"10.1016","volume":"303","author":[{"given":"Marzena","family":"Brinkmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Yun (Kent)","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osha","family":"Roopnarine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha L.","family":"Yuen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaja","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razvan L.","family":"Cornea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-2286","authenticated-orcid":false,"given":"Robyn T.","family":"Rebbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney C.","family":"Aldrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2025.118408_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2021.100412","article-title":"The transmembrane peptide DWORF activates SERCA2a via dual mechanisms","volume":"296","author":"Li","year":"2021","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2025.118408_bib2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bbrc.2023.01.041","article-title":"Interaction of DWORF with SERCA and PLB as determined by EPR spectroscopy","volume":"645","author":"Rustad","year":"2023","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejmech.2025.118408_bib3","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2023.1185261","article-title":"Targeting calcium regulators as therapy for heart failure: focus on the sarcoplasmic reticulum Ca-ATPase pump","volume":"10","author":"Kho","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"10.1016\/j.ejmech.2025.118408_bib4","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.3390\/jcm11072020","article-title":"An up-to-date article regarding particularities of drug treatment in patients with chronic heart failure","volume":"11","author":"Buda","year":"2022","journal-title":"J. Clin. Med."},{"key":"10.1016\/j.ejmech.2025.118408_bib5","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-29685-z","article-title":"Targeting protein-protein interactions for therapeutic discovery via FRET-based high-throughput screening in living cells","volume":"8","author":"Stroik","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2025.118408_bib6","first-page":"13","article-title":"Polyphenolic compounds activate SERCA1a and attenuate Methylglyoxal- and palmitate-induced impairment in pancreatic INS-1E beta cells","author":"Heger","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.ejmech.2025.118408_bib7","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejphar.2013.02.045","article-title":"Ellagic acid and gingerol, activators of the sarco-endoplasmic reticulum Ca(2)(+)-ATPase, ameliorate diabetes mellitus-induced diastolic dysfunction in isolated murine ventricular myocardia","volume":"706","author":"Namekata","year":"2013","journal-title":"Eur. J. Pharmacol."},{"issue":"2","key":"10.1016\/j.ejmech.2025.118408_bib8","doi-asserted-by":"crossref","DOI":"10.26508\/lsa.202302278","article-title":"A dual-targeted drug inhibits cardiac ryanodine receptor Ca2+ leak but activates SERCA2a Ca2+ uptake","volume":"7","author":"Wegener","year":"2023","journal-title":"Life Sci Alliance"},{"key":"10.1016\/j.ejmech.2025.118408_bib9","doi-asserted-by":"crossref","DOI":"10.1002\/cmdc.202400913","article-title":"Machine learning-driven discovery of structurally related natural products as activators of the cardiac calcium pump SERCA2a","volume":"20","author":"Cruz-Cortes","year":"2025","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2025.118408_bib10","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1124\/jpet.108.138701","article-title":"Modulation of sarcoplasmic reticulum function by PST2744 [istaroxime; (E,Z)-3-((2-aminoethoxy)imino) androstane-6,17-dione hydrochloride)] in a pressure-overload heart failure model","volume":"326","author":"Rocchetti","year":"2008","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejmech.2025.118408_bib11","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1124\/jpet.122.001335","article-title":"Istaroxime metabolite PST3093 selectively stimulates SERCA2a and reverses disease-induced changes in cardiac function","volume":"384","author":"Arici","year":"2023","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejmech.2025.118408_bib12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12967-024-04874-9","article-title":"Selective SERCA2a activator as a candidate for chronic heart failure therapy","volume":"22","author":"Arici","year":"2024","journal-title":"J. Transl. Med."},{"key":"10.1016\/j.ejmech.2025.118408_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.vph.2024.107295","article-title":"Istaroxime follow-on compounds: a new class of selective SERCA2a activators for chronic heart failure treatment","volume":"155","author":"Arici","year":"2024","journal-title":"Vasc. Pharmacol."},{"key":"10.1016\/j.ejmech.2025.118408_bib14","doi-asserted-by":"crossref","first-page":"pgad453","DOI":"10.1093\/pnasnexus\/pgad453","article-title":"Mechanisms for cardiac calcium pump activation by its substrate and a synthetic allosteric modulator using fluorescence lifetime imaging","volume":"3","author":"Seflova","year":"2024","journal-title":"PNAS Nexus"},{"issue":"15","key":"10.1016\/j.ejmech.2025.118408_bib15","doi-asserted-by":"crossref","first-page":"16306","DOI":"10.1021\/acs.jmedchem.5c01192","article-title":"SAR-guided development of small-molecule SERCA2a activators: discovery of potent indoline, benzofuran, and benzodioxole analogs for cardiovascular applications","volume":"68","author":"Ard","year":"2025","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118408_bib16","doi-asserted-by":"crossref","DOI":"10.1002\/cmdc.202400763","article-title":"Quinoline- and pyrimidine-based allosteric modulators of the sarco\/endoplasmic reticulum calcium ATPase","volume":"20","author":"Paula","year":"2025","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2025.118408_bib17","doi-asserted-by":"crossref","first-page":"7324","DOI":"10.1021\/acs.jmedchem.2c00347","article-title":"Highly selective SERCA2a activators: Preclinical development of a congeneric group of first-in-class drug leads against heart failure","volume":"65","author":"Luraghi","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118408_bib18","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.3390\/biom12121789","article-title":"A large-scale high-throughput screen for modulators of SERCA activity","volume":"12","author":"Bidwell","year":"2022","journal-title":"Biomolecules"},{"key":"10.1016\/j.ejmech.2025.118408_bib19","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.bpj.2022.12.002","article-title":"New N-aryl-N-alkyl-thiophene-2-carboxamide compound enhances intracellular Ca(2+) dynamics by increasing SERCA2a Ca(2+) pumping","volume":"122","author":"Nikolaienko","year":"2023","journal-title":"Biophys. J."},{"key":"10.1016\/j.ejmech.2025.118408_bib20","doi-asserted-by":"crossref","first-page":"3849","DOI":"10.1021\/jo960057x","article-title":"Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination Procedures(1)","volume":"61","author":"Abdel-Magid","year":"1996","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.ejmech.2025.118408_bib21","doi-asserted-by":"crossref","first-page":"5198","DOI":"10.1021\/jo300734r","article-title":"Rotamers or diastereomers? An overlooked NMR solution","volume":"77","author":"Hu","year":"2012","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.ejmech.2025.118408_bib22","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-023-37704-x","article-title":"Fluorescence lifetime FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators","volume":"13","author":"Roopnarine","year":"2023","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2025.118408_bib23","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1177\/1087057112456878","article-title":"High-throughput FRET assay yields allosteric SERCA activators","volume":"18","author":"Cornea","year":"2013","journal-title":"J. Biomol. Screen"},{"key":"10.1016\/j.ejmech.2025.118408_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.jmb.2025.169200","article-title":"Allosteric modulation of SERCA pumps in health and disease: structural dynamics, posttranslational modifications, and therapeutic potential","volume":"437","author":"Viskupicova","year":"2025","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ejmech.2025.118408_bib25","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1177\/1087057113510740","article-title":"Discovery of enzyme modulators via high-throughput time-resolved FRET in living cells","volume":"19","author":"Gruber","year":"2014","journal-title":"J. Biomol. Screen"},{"key":"10.1016\/j.ejmech.2025.118408_bib26","doi-asserted-by":"crossref","first-page":"3940","DOI":"10.1021\/bi00435a047","article-title":"Conformational transitions in the calcium adenosinetriphosphatase studied by time-resolved fluorescence resonance energy transfer","volume":"28","author":"Birmachu","year":"1989","journal-title":"Biochemistry"},{"key":"10.1016\/j.ejmech.2025.118408_bib27","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/0005-2736(80)90199-6","article-title":"Highly purified sarcoplasmic reticulum vesicles are devoid of Ca2+-independent ('basal') ATPase activity","volume":"599","author":"Fernandez","year":"1980","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ejmech.2025.118408_bib28","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.3390\/cells9051170","article-title":"Live-cell cardiac-specific high-throughput screening platform for drug-like molecules that enhance Ca(2+) transport","volume":"9","author":"Schaaf","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.ejmech.2025.118408_bib29","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/0006-2952(94)90520-7","article-title":"Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance","volume":"47","author":"Houston","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejmech.2025.118408_bib30","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1124\/dmd.105.004259","article-title":"A unified model for predicting human hepatic, metabolic clearance from in vitro intrinsic clearance data in hepatocytes and microsomes","volume":"33","author":"Riley","year":"2005","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.ejmech.2025.118408_bib31","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.neuro.2023.07.001","article-title":"CDN1163, a SERCA activator, causes intracellular Ca(2+) leak, mitochondrial hyperpolarization and cell cycle arrest in mouse neuronal N2A cells","volume":"98","author":"Huang","year":"2023","journal-title":"Neurotoxicology"},{"key":"10.1016\/j.ejmech.2025.118408_bib32","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00210-018-01601-2","article-title":"Enhancing tetrandrine cytotoxicity in human lung carcinoma A549 cells by suppressing mitochondrial ATP production","volume":"392","author":"Chow","year":"2019","journal-title":"Naunyn-Schmiedebergs Arch Pharmacol"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425011730?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425011730?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:54:05Z","timestamp":1781326445000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425011730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":32,"alternative-id":["S0223523425011730"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118408","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Development of activators for SERCA2a for heart failure treatments","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118408","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"118408"}}