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β-肾上腺素受体历险记:对最广泛研究的 G 蛋白偶联受体之一进行令人痛苦的研究的长期职业生涯。

Adventures with the β-adrenoceptor Receptor: A Career Long Interest in Agonising One of the Most Widely Studied GPCRs.

机构信息

Novartis Oncology Disease, Basel, CH-4056, Switzerland.

出版信息

Chimia (Aarau). 2024 Aug 21;78(7-8):483-498. doi: 10.2533/chimia.2024.483.

Abstract

Drug discovery is a multi-disciplinary effort in which groups with expertise in a range of areas combine in a unified way to achieve a common goal: to deliver a clinical candidate to evaluate a hypothesis for improving human health. As a medicinal chemist this environment has provided multiple opportunities to be involved in cross-discipline interactions that have been both rewarding and led to outcomes that would not have been possible without an intimate interdisciplinary curiosity. Within this article I aim to share some of my experiences with the β2-adrenoceptor that have fostered such synergistic relationships with several disciplines, but in particular with in vitro pharmacologists looking at different ways to stimulate this G protein-coupled receptor (GPCR). This interest now spans over a quarter of a century and has been intertwined with the delivery of three clinical candidates.

摘要

药物发现是一项多学科的努力,具有不同专业知识的团队以统一的方式结合在一起,以实现一个共同的目标:提供一个临床候选物来评估改善人类健康的假设。作为一名药物化学家,这种环境为我提供了多次参与跨学科互动的机会,这些互动既有收获,又带来了没有亲密的跨学科好奇心就不可能实现的结果。在本文中,我旨在分享我在β2-肾上腺素能受体方面的一些经验,这些经验促进了与几个学科的协同关系,特别是与体外药理学家一起研究刺激这种 G 蛋白偶联受体(GPCR)的不同方法。这种兴趣现在已经跨越了四分之一个世纪,并与三个临床候选物的交付交织在一起。

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