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从昆虫中高保真受体介导的转导机制中获取药物发现的潜在见解。

Potential insight for drug discovery from high fidelity receptor-mediated transduction mechanisms in insects.

作者信息

Raffa Robert B, Raffa Kenneth F

机构信息

Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA.

出版信息

Expert Opin Drug Discov. 2011 Oct 1;6(10):1091-1101. doi: 10.1517/17460441.2011.611497.

DOI:10.1517/17460441.2011.611497
PMID:21984882
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3185357/
Abstract

INTRODUCTION

There is a pervasive and growing concern about the small number of new pharmaceutical agents. There are many proposed explanations for this trend that do not involve the drug-discovery process per se, but the discovery process itself has also come under scrutiny. If the current paradigms are indeed not working, where are novel ideas to come from? Perhaps it is time to look to novel sources. AREAS COVERED: The receptor-signaling and 2(nd)-messenger transduction processes present in insects are quite similar to those in mammals (involving G proteins, ion channels, etc.). However, a review of these systems reveals an unprecedented degree of high potency and receptor selectivity to an extent greater than that modeled in most current drug-discovery approaches. EXPERT OPINION: A better understanding of insect receptor pharmacology could stimulate novel theoretical and practical ideas in mammalian pharmacology (drug discovery) and, conversely, the application of pharmacology and medicinal chemistry principles could stimulate novel advances in entomology (safer and more targeted control of pest species).

摘要

引言

人们对新型药物制剂数量稀少的问题普遍且日益担忧。对于这一趋势有许多提出的解释,这些解释并不涉及药物发现过程本身,但发现过程本身也受到了审视。如果当前的范式确实不起作用,新想法将从何而来?也许是时候寻找新的来源了。

涵盖领域

昆虫体内存在的受体信号传导和第二信使转导过程与哺乳动物中的非常相似(涉及G蛋白、离子通道等)。然而,对这些系统的综述揭示了一种前所未有的高效能和受体选择性程度,其程度超过了大多数当前药物发现方法所模拟的程度。

专家意见

更好地理解昆虫受体药理学可以激发哺乳动物药理学(药物发现)中的新理论和实践想法,反之,药理学和药物化学原理的应用可以激发昆虫学中的新进展(对害虫物种进行更安全、更有针对性的控制)。

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