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用低效的指标提高成功的可信度。

Improving the plausibility of success with inefficient metrics.

作者信息

Shultz Michael D

机构信息

Novartis Institutes for Biomedical Research, Inc. , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

出版信息

ACS Med Chem Lett. 2013 Nov 21;5(1):2-5. doi: 10.1021/ml4004638. eCollection 2014 Jan 9.

DOI:10.1021/ml4004638
PMID:24900765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4027587/
Abstract

To increase the probability of success in drug discovery, the concept of drug-like properties was introduced. Efficiency metrics that normalize potency against these properties could help reach drug-like space more efficiently. Potential reasons for the inefficient use of metrics and suboptimal decision making are discussed.

摘要

为了提高药物研发成功的概率，引入了类药性质的概念。针对这些性质对效力进行归一化的效率指标有助于更高效地进入类药空间。文中讨论了指标使用效率低下和决策欠佳的潜在原因。

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本文引用的文献

1
The thermodynamic basis for the use of lipophilic efficiency (LipE) in enthalpic optimizations.亲脂效率（LipE）在焓优化中应用的热力学基础。
Bioorg Med Chem Lett. 2013 Nov 1;23(21):5992-6000. doi: 10.1016/j.bmcl.2013.08.030. Epub 2013 Aug 14.
2
Setting expectations in molecular optimizations: Strengths and limitations of commonly used composite parameters.在分子优化中设定预期：常用综合参数的优缺点。
Bioorg Med Chem Lett. 2013 Nov 1;23(21):5980-91. doi: 10.1016/j.bmcl.2013.08.029. Epub 2013 Aug 13.
3
Inflation of correlation in the pursuit of drug-likeness.追求类药性时相关性的膨胀。
J Comput Aided Mol Des. 2013 Jan;27(1):1-13. doi: 10.1007/s10822-012-9631-5. Epub 2013 Jan 10.
4
Relating molecular properties and in vitro assay results to in vivo drug disposition and toxicity outcomes.将分子性质和体外试验结果与体内药物处置和毒性结果相关联。
J Med Chem. 2012 Jul 26;55(14):6455-66. doi: 10.1021/jm300684u. Epub 2012 Jul 5.
5
Medicinal chemistry matters - a call for discipline in our discipline.药学化学至关重要——呼吁我们学科加强纪律性。
Drug Discov Today. 2012 Jun;17(11-12):538-43. doi: 10.1016/j.drudis.2012.01.010. Epub 2012 Jan 25.
6
Ligand efficiency: a useful metric for lead selection.配体效率：先导化合物筛选的有用指标。
Drug Discov Today. 2004 May 15;9(10):430-1. doi: 10.1016/S1359-6446(04)03069-7.
7
A comparison of physiochemical property profiles of development and marketed oral drugs.已上市口服药物与处于研发阶段口服药物的理化性质概况比较。
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