Human F-ATP synthase as a drug target

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research Pub Date : 2024-09-19 DOI:10.1016/j.phrs.2024.107423

Christoph Gerle , Chimari Jiko , Atsuki Nakano , Ken Yokoyama , Chai C. Gopalasingam , Hideki Shigematsu , Kazuhiro Abe

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引用次数: 0

Abstract

Practical and conceptual barriers have kept human F-ATP synthase out of reach as a target for the treatment of human diseases. Although this situation has persisted for decades, it may change in the near future. In this review the principal functionalities of human F-ATP synthase--proton motive force / ATP interconversion, membrane bending and mitochondrial permeability transition--are surveyed in the context of their respective potential for pharmaceutical intervention. Further, the technical requirements necessary to allow drug designs that are effective at the multiple levels of functionality and modality of human F-ATP synthase are discussed. The structure-based development of gastric proton pump inhibitors is used to exemplify what might be feasible for human F-ATP synthase. And finally, four structural regions of the human F-ATP synthase are examined as potential sites for the development of structure based drug development.

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作为药物靶点的人类 F-ATP 合酶

由于实际操作和概念上的障碍，人类 F-ATP 合成酶一直未能成为治疗人类疾病的靶点。虽然这种情况已经持续了几十年，但在不久的将来可能会改变。在这篇综述中，我们结合人类 F-ATP 合成酶的主要功能--质子动力/ATP 相互转化、膜弯曲和线粒体通透性转换--对它们各自的药物干预潜力进行了研究。此外，还讨论了在人类 F-ATP 合成酶的多层次功能和模式下进行有效药物设计所需的技术要求。以基于结构的胃质子泵抑制剂的开发为例，说明人类 F-ATP 合成酶的可行性。最后，对人类 F-ATP 合成酶的四个结构区域进行了研究，将其作为开发基于结构的药物的潜在部位。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacological research 医学-药学

CiteScore

18.70

自引率

3.20%

发文量

491

审稿时长

8 days

期刊介绍： Pharmacological Research publishes cutting-edge articles in biomedical sciences to cover a broad range of topics that move the pharmacological field forward. Pharmacological research publishes articles on molecular, biochemical, translational, and clinical research (including clinical trials); it is proud of its rapid publication of accepted papers that comprises a dedicated, fast acceptance and publication track for high profile articles.