Drug-like annotation and duplicate analysis of a 23-supplier chemical database totalling 2.7 million compounds
Drug-like annotation and duplicate analysis of a 23-supplier chemical database totalling 2.7 million compounds
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DOI：
10.1021/ci034260m
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发表时间：
2004-03-01
期刊：
影响因子：
--
通讯作者：
Hubbard, RE
中科院分区：
文献类型：
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作者：
Baurin, N;Baker, R;Hubbard, RE
我们已经实现了五个基于ID和2D分子描述符的类药物过滤器，并应用它们来表征商业上可获得的化合物的类药物性质。除了之前发表的过滤器(Lipinski和Veber)外，我们还根据一个药物化学家小组起草的化学特征列表，实现了一个药物化学可处理性过滤器。基于水的溶解度模型(>；1um)和基于CaCO-2被动膜渗透率的模型(>；10 nm/S)，在内部设计了一种过滤器。从23家化合物供应商那里整理了一个包含270万种化合物的库，并用这些过滤器进行了分析，突出了高度亲脂化合物的趋势。该文库包含160万个独特的结构，其中37%(607223)通过了所有五个药物样过滤器。23家供应商中没有一家提供类药物子集的所有成员，强调将来自不同化合物供应商的化合物视为药物发现的多样性来源的好处。
We have implemented five drug-like filters, based on ID and 2D molecular descriptors, and applied them to characterize the drug-like properties of commercially available chemical compounds. In addition to previously published filters (Lipinski and Veber), we implemented a filter for medicinal chemistry tractability based on lists of chemical features drawn up by a panel of medicinal chemists. A filter based on the modeling of aqueous solubility (>1 muM) was derived in-house, as well as another based on the modeling of Caco-2 passive membrane permeability (>10 nm/s). A library of 2.7 million compounds was collated from the 23 compound suppliers and analyzed with these filters, highlighting a tendency toward highly lipophilic compounds. The library contains 1.6M unique structures, of which 37% (607 223) passed all five drug-like filters. None of the 23 suppliers provides all the members of the drug-like subset, emphasizing the benefit of considering compounds from various compound suppliers as a source of diversity for drug discovery.