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探索 DrugCentral:从分子结构到临床效应。

Exploring DrugCentral: from molecular structures to clinical effects.

机构信息

Department of Computational Chemistry, "Coriolan Dragulescu" Institute of Chemistry, Timisoara, Romania.

Translational Informatics Division, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA.

出版信息

J Comput Aided Mol Des. 2023 Dec;37(12):681-694. doi: 10.1007/s10822-023-00529-x. Epub 2023 Sep 14.

Abstract

DrugCentral, accessible at https://drugcentral.org , is an open-access online drug information repository. It covers over 4950 drugs, incorporating structural, physicochemical, and pharmacological details to support drug discovery, development, and repositioning. With around 20,000 bioactivity data points, manual curation enhances information from several major digital sources. Approximately 724 mechanism-of-action (MoA) targets offer updated drug target insights. The platform captures clinical data: over 14,300 on- and off-label uses, 27,000 contraindications, and around 340,000 adverse drug events from pharmacovigilance reports. DrugCentral encompasses information from molecular structures to marketed formulations, providing a comprehensive pharmaceutical reference. Users can easily navigate basic drug information and key features, making DrugCentral a versatile, unique resource. Furthermore, we present a use-case example where we utilize experimentally determined data from DrugCentral to support drug repurposing. A minimum activity threshold t should be considered against novel targets to repurpose a drug. Analyzing 1156 bioactivities for human MoA targets suggests a general threshold of 1 µM: t = 6 when expressed as - log[Activity(M)]). This applies to 87% of the drugs. Moreover, t can be refined empirically based on water solubility (S): t = 3 - logS, for logS < - 3. Alongside the drug repurposing classification scheme, which considers intellectual property rights, market exclusivity protections, and market accessibility, DrugCentral provides valuable data to prioritize candidates for drug repurposing programs efficiently.

摘要

DrugCentral 可在 https://drugcentral.org 上访问,是一个开放获取的在线药物信息库。它涵盖了超过 4950 种药物,包含结构、物理化学和药理学细节,以支持药物发现、开发和重新定位。拥有约 20000 个生物活性数据点,人工策展增强了来自几个主要数字来源的信息。大约 724 个作用机制 (MoA) 靶点提供了更新的药物靶点见解。该平台捕获了临床数据:超过 14300 种标签内和标签外用途、27000 种禁忌症和约 340000 种药物警戒报告中的不良药物事件。DrugCentral 包含从分子结构到市售制剂的信息,提供了全面的药物参考。用户可以轻松浏览基本药物信息和关键功能,使 DrugCentral 成为一个多功能、独特的资源。此外,我们还提供了一个用例示例,我们利用从 DrugCentral 中确定的实验数据来支持药物重新定位。针对新靶点重新定位药物时,应考虑最小活性阈值 t。分析 1156 个人类 MoA 靶点的生物活性表明,一般阈值为 1µM:当表示为 -log[Activity(M)]时,t=6)。这适用于 87%的药物。此外,t 可以根据水溶性 (S) 进行经验性地细化:t=3 - logS,对于 logS < -3。除了考虑知识产权、市场独占保护和市场可及性的药物重新定位分类方案外,DrugCentral 还提供了有价值的数据,可有效优先考虑药物重新定位计划的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5841/10692006/d978264c262f/10822_2023_529_Fig1_HTML.jpg

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