A comprehensive map of molecular drug targets.
A comprehensive map of molecular drug targets.
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DOI：
10.1038/nrd.2016.230
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Overington JP
中科院分区：
文献类型：
--
作者：
Santos R;Ursu O;Gaulton A;Bento AP;Donadi RS;Bologa CG;Karlsson A;Al-Lazikani B;Hersey A;Oprea TI;Overington JP
基于机制的药物发现的成功取决于药物靶点的定义。当我们试图将药物反应与遗传变异联系起来，理解分层的临床疗效和安全性，合理化相同治疗类别药物之间的差异，并预测患者亚组中的药物效用时，这个定义变得更加重要。然而，在文献中，药物靶点通常定义得很差，无论是对于已上市的药物还是对于发现和开发中的潜在治疗剂。在这里，我们提出了一个更新的综合地图的分子靶点批准的药物。我们总共收集了893种人类和病原体衍生的生物分子，其中1，578种美国FDA批准的药物起作用。这些生物分子包括667种人类基因组衍生的蛋白质，这些蛋白质被用于治疗人类疾病的药物靶向。对这些药物靶点的分析表明，在疾病领域，特权靶家族继续占据主导地位，但新的一流机制也在增长，特别是在肿瘤学领域。我们探讨了生物活性类别和临床成功之间的关系，以及人类和动物模型之间以及病原体和人类基因组之间的直系同源物的存在。通过三个独立团队的合作，我们强调了在准确定义分子治疗靶点方面的一些持续挑战，并提出了消除分子药理学和药物疗效复杂性的惯例。
The success of mechanism-based drug discovery depends on the definition of the drug target. This definition becomes even more important as we try to link drug response to genetic variation, understand stratified clinical efficacy and safety, rationalize the differences between drugs in the same therapeutic class and predict drug utility in patient subgroups. However, drug targets are often poorly defined in the literature, both for launched drugs and for potential therapeutic agents in discovery and development. Here, we present an updated comprehensive map of molecular targets of approved drugs. We curate a total of 893 human and pathogen-derived biomolecules through which 1,578 US FDA-approved drugs act. These biomolecules include 667 human-genome-derived proteins targeted by drugs for human disease. Analysis of these drug targets indicates the continued dominance of privileged target families across disease areas, but also the growth of novel first-in-class mechanisms, particularly in oncology. We explore the relationships between bioactivity class and clinical success, as well as the presence of orthologues between human and animal models and between pathogen and human genomes. Through the collaboration of three independent teams, we highlight some of the ongoing challenges in accurately defining the targets of molecular therapeutics and present conventions for deconvoluting the complexities of molecular pharmacology and drug efficacy.
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DOI：
10.4137/cmc.s8445
发表时间：
2013
期刊：
Clinical Medicine Insights. Cardiology
影响因子：
--
作者：
Heijman J;Heusch G;Dobrev D
通讯作者：
Dobrev D
DOI：
10.1089/mdr.1996.2.183
发表时间：
1996-06-01
期刊：
MICROBIAL DRUG RESISTANCE-MECHANISMS EPIDEMIOLOGY AND DISEASE
影响因子：
--
作者：
Krauss, J;vanderLinden, M;Hakenbeck, R
通讯作者：
Hakenbeck, R
依伐布拉丁与HCN4通道结合的分子位点的鉴定。
影响因子：
3.7
作者：
Bucchi A;Baruscotti M;Nardini M;Barbuti A;Micheloni S;Bolognesi M;DiFrancesco D
通讯作者：
DiFrancesco D
影响因子：
46.9
作者：
Drews, J
通讯作者：
Drews, J
影响因子：
14.9
作者：
Chen, X;Ji, ZL;Chen, YZ
通讯作者：
Chen, YZ