Chemical structural novelty: on-targets and off-targets.
Chemical structural novelty: on-targets and off-targets.
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DOI：
10.1021/jm200666a
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发表时间：
2011-10-13
影响因子：
7.3
通讯作者：
Jain, Ajay N.
中科院分区：
文献类型：
--
作者：
Yera, Emmanuel R.;Cleves, Ann E.;Jain, Ajay N.
可以基于 2D 拓扑结构考虑因素和基于与结合直接相关的 3D 特征来定量比较药物结构。提出了一个结合多种相似性计算的框架，及其对 358 种具有重叠药理学的药物的系统应用。给定一个新分子以及一组具有某些生物效应的分子，系统会根据与已知分子组的比较生成一个分数，反映 2D 相似性、3D 相似性或它们的组合。对于主要目标的预测，3D 相对于 2D 的好处相对较小，但对于脱靶的预测，附加的好处很大。除了评估预测之外，还研究了化学相似性和药理学新颖性之间的关系。具有高 3D 相似性但低 2D 相似性的药物对（即新型支架）被证明更有可能在特定蛋白质靶标调节方面表现出药理学相关差异。
Drug structures may be quantitatively compared based on 2D topological structural considerations and based on 3D characteristics directly related to binding. A framework for combining multiple similarity computations is presented along with its systematic application to 358 drugs with overlapping pharmacology. Given a new molecule along with a set of molecules sharing some biological effect, a single score based on comparison to the known set is produced, reflecting either 2D similarity, 3D similarity, or their combination. For prediction of primary targets, the benefit of 3D over 2D was relatively small, but for prediction of off-targets, the added benefit was large. In addition to assessing prediction, the relationship between chemical similarity and pharmacological novelty was studied. Drug pairs that shared high 3D similarity but low 2D similarity (i.e. a novel scaffold) were shown to be much more likely to exhibit pharmacologically relevant differences in terms of specific protein target modulation.
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影响因子：
4.2
作者：
Brown, EG;Wood, L;Wood, S
通讯作者：
Wood, S
DOI：
10.1021/ci970437z
发表时间：
1998-05-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
Flower, DR
通讯作者：
Flower, DR
影响因子：
7.3
作者：
Efange, SMN;Kamath, AP;Parsons, SM
通讯作者：
Parsons, SM
影响因子：
4.7
作者：
LIN, SC;OLSON, KC;RICHELSON, E
通讯作者：
RICHELSON, E
影响因子：
9.9
作者：
Kuhn M;Campillos M;Letunic I;Jensen LJ;Bork P
通讯作者：
Bork P