Selatogrel: Potential to redefine timely anti-platelet intervention.

IF 7.7 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Rudy N Zalzal, Peter P Salem, Ali H Dakroub, Ali H Eid
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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.

塞拉托格雷:重新定义及时抗血小板干预的潜力。
急性冠状动脉综合征(ACS)包括一些心脏病,导致冠状动脉灌注突然减少,心肌细胞坏死或其风险增加。这种病理是心血管疾病的主要负担。ACS的发病机制和临床表现主要是由于心肌灌注不足引起的冠状血管阻塞,通常是由于动脉粥样硬化斑块破裂和随后的血栓形成。双重抗血小板治疗(DAPT),包括阿司匹林和P2Y12受体拮抗剂,长期以来一直是ACS治疗的支柱。尽管如此,传统DAPT药物在药代动力学(PK)和药效学(PD)方面的局限性仍然存在。Selatogrel (ACT-246475)是一种新型P2Y12拮抗剂,目前正在进行III期临床试验,有望彻底改变ACS的治疗。这种高选择性和有效的2-苯基嘧啶-4-羧酰胺类似物皮下施用。因此,它为ACS患者提供了即时干预。重要的是,西拉格雷具有显著的快速起效和良好的安全性。这些优点使西拉格雷成为院前自我给药ACS治疗的有希望的候选者,有可能优化减少总缺血时间。在成功完成了几项I期和II期试验后,塞拉托格雷目前正在进行III期评估,以进一步阐明其安全性和有效性。后续的研究将有助于支持或完善其治疗特性。
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来源期刊
CiteScore
15.40
自引率
12.30%
发文量
270
审稿时长
2.0 months
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.
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