Rudy N Zalzal, Peter P Salem, Ali H Dakroub, Ali H Eid
{"title":"Selatogrel: Potential to redefine timely anti-platelet intervention.","authors":"Rudy N Zalzal, Peter P Salem, Ali H Dakroub, Ali H Eid","doi":"10.1111/bph.70203","DOIUrl":null,"url":null,"abstract":"<p><p>Acute coronary syndrome (ACS) encompasses a number of heart diseases that cause a sudden decrease in coronary perfusion, precipitating cardiomyocyte necrosis or heightened risk thereof. This pathology is a major burden of cardiovascular disease. The etiopathogenesis and clinical manifestation of ACS are predominantly attributable to myocardial hypoperfusion consequent, to coronary vessel occlusion, typically resulting from atherosclerotic plaque rupture and subsequent thrombosis. Dual antiplatelet therapy (DAPT), comprising aspirin and a P2Y<sub>12</sub> receptor antagonist, has long been the mainstay of ACS management. Notwithstanding, limitations in the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of conventional DAPT agents persist. Selatogrel (ACT-246475), a novel P2Y<sub>12</sub> antagonist currently undergoing Phase III clinical trial, is poised to revolutionise ACS treatment. This highly selective and potent 2-phenylpyrimidine-4-carboxamide analogue is administered subcutaneously. As such, it affords immediate intervention in ACS patients. Importantly, selatogrel has a remarkably rapid onset of action and a favourable safety profile. These advantages render selatogrel a promising candidate for pre-hospital, self-administered ACS treatment, potentially optimising the reduction of total ischaemic time. Having successfully completed several Phase I and Phase II trials, selatogrel is currently undergoing Phase III evaluation to further elucidate its safety and efficacy. Subsequent investigations will serve to support or refine its therapeutic attributes.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"British Journal of Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/bph.70203","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Acute coronary syndrome (ACS) encompasses a number of heart diseases that cause a sudden decrease in coronary perfusion, precipitating cardiomyocyte necrosis or heightened risk thereof. This pathology is a major burden of cardiovascular disease. The etiopathogenesis and clinical manifestation of ACS are predominantly attributable to myocardial hypoperfusion consequent, to coronary vessel occlusion, typically resulting from atherosclerotic plaque rupture and subsequent thrombosis. Dual antiplatelet therapy (DAPT), comprising aspirin and a P2Y12 receptor antagonist, has long been the mainstay of ACS management. Notwithstanding, limitations in the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of conventional DAPT agents persist. Selatogrel (ACT-246475), a novel P2Y12 antagonist currently undergoing Phase III clinical trial, is poised to revolutionise ACS treatment. This highly selective and potent 2-phenylpyrimidine-4-carboxamide analogue is administered subcutaneously. As such, it affords immediate intervention in ACS patients. Importantly, selatogrel has a remarkably rapid onset of action and a favourable safety profile. These advantages render selatogrel a promising candidate for pre-hospital, self-administered ACS treatment, potentially optimising the reduction of total ischaemic time. Having successfully completed several Phase I and Phase II trials, selatogrel is currently undergoing Phase III evaluation to further elucidate its safety and efficacy. Subsequent investigations will serve to support or refine its therapeutic attributes.
期刊介绍:
The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries.
Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues.
In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.