Lessons learnt from assembling screening libraries for drug discovery for neglected diseases.
Lessons learnt from assembling screening libraries for drug discovery for neglected diseases.
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DOI：
10.1002/cmdc.200700139
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发表时间：
2008-03
期刊：
影响因子：
3.4
通讯作者：
Wyatt, Paul Graham
中科院分区：
文献类型：
--
作者：
Brenk, Ruth;Schipani, Alessandro;James, Daniel;Krasowski, Agata;Gilbert, Ian Hugh;Frearson, Julie;Wyatt, Paul Graham
关键词：
为了能够建立针对被忽视疾病的药物发现操作，从230万种市售化合物中选择了222 552种化合物用于计算机库，57 438种化合物用于多样化的一般筛选库，1 697种化合物用于聚焦激酶集。编译这些库需要一个强大的化合物选择策略。不需要的基团的规则进行了定义，并建立了选择标准，以丰富的铅样化合物，促进直接的结构-活性关系的探索。此外，进行文献和专利综述以提取激酶抑制剂的关键识别元件（“核心片段”），以组装用于激酶的命中发现的聚焦文库。一般筛选文库的计算和实验表征显示，所选化合物1）跨越宽范围的铅样空间，2）显示高度的结构完整性和纯度，和3）证明用于生物化学筛选目的的适当溶解度。本研究的影响，特别是在资源有限的学术环境中，化合物的选择，被认为是。
To enable the establishment of a drug discovery operation for neglected diseases, out of 2.3 million commercially available compounds 222 552 compounds were selected for an in silico library, 57 438 for a diverse general screening library, and 1 697 compounds for a focused kinase set. Compiling these libraries required a robust strategy for compound selection. Rules for unwanted groups were defined and selection criteria to enrich for lead-like compounds which facilitate straightforward structure–activity relationship exploration were established. Further, a literature and patent review was undertaken to extract key recognition elements of kinase inhibitors (“core fragments”) to assemble a focused library for hit discovery for kinases. Computational and experimental characterisation of the general screening library revealed that the selected compounds 1) span a broad range of lead-like space, 2) show a high degree of structural integrity and purity, and 3) demonstrate appropriate solubility for the purposes of biochemical screening. The implications of this study for compound selection, especially in an academic environment with limited resources, are considered.
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影响因子：
2.7
作者：
Holloway GA;Baell JB;Fairlamb AH;Novello PM;Parisot JP;Richardson J;Watson KG;Street IP
通讯作者：
Street IP
DOI：
10.1021/ci034260m
发表时间：
2004-03-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
Baurin, N;Baker, R;Hubbard, RE
通讯作者：
Hubbard, RE
影响因子：
120.1
作者：
Haffner, ME;Whitley, J;Moses, M
通讯作者：
Moses, M
影响因子：
7.3
作者：
Makara, Gergely M.
通讯作者：
Makara, Gergely M.
影响因子：
2.7
作者：
Martyn, Derek C.;Jones, Deuan C.;Clardy, Jon
通讯作者：
Clardy, Jon