PAINS: Relevance to Tool Compound Discovery and Fragment-Based Screening
PAINS: Relevance to Tool Compound Discovery and Fragment-Based Screening
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DOI：
10.1071/ch13551
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发表时间：
2013-01-01
影响因子：
1.1
通讯作者：
Nikolakopoulos, George
中科院分区：
文献类型：
--
作者：
Baell, Jonathan B.;Ferrins, Lori;Nikolakopoulos, George
泛测定干扰化合物（PAINS）在任何生物测定中都很容易发现，并且似乎可以提供选择性和可优化的命中。最常见的疼痛可以通过其结构容易地识别。然而，有些化合物与疼痛过滤器无法特异性识别的疼痛非常相似。此外，高反应性化合物未在PAINS过滤器中编码，因为它们被排除在用于开发过滤器的高通量筛选（HTS）文库之外，因此从未存在以提供指示数据。该区域的复合并发症是疼痛化合物偶尔可能作为进展的可行起点。尽管有这样一个偶然的例子，但文献中充斥着大量未能取得进展的化合物的例子，这些化合物可能一开始就不是可优化的，也不是有用的工具化合物。因此，应非常谨慎和勤奋地将具有已知PAINS核心的化合物进展到药物化学优化，如果有的话，因为发现命中是不可进展的可能性非常高，通常是在显著浪费资源之后。
Pan assay interference compounds (PAINS) are readily discovered in any bioassay and can appear to give selective and optimisable hits. The most common PAINS can be readily recognised by their structure. However, there are compounds that closely resemble PAINS that are not specifically recognised by the PAINS filters. In addition, highly reactive compounds are not encoded for in the PAINS filters because they were excluded from the high-throughput screening (HTS) library used to develop the filters and so were never present to provide indicting data. A compounding complication in the area is that very occasionally a PAINS compound may serve as a viable starting point for progression. Despite such an occasional example, the literature is littered with an overwhelming number of examples of compounds that fail to progress and were probably not optimisable in the first place, nor useful tool compounds. Thus it is with great caution and diligence that compounds possessing a known PAINS core should be progressed through to medicinal chemistry optimisation, if at all, as the chances are very high that the hits will be found to be non-progressable, often after a significant waste of resources.