An information-intensive approach to the molecular pharmacology of cancer
An information-intensive approach to the molecular pharmacology of cancer
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DOI：
10.1126/science.275.5298.343
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发表时间：
1997-01-17
期刊：
影响因子：
56.9
通讯作者：
Paull, KD
中科院分区：
文献类型：
--
作者：
Weinstein, JN;Myers, TG;Paull, KD
自1990年以来，美国国家癌症研究所（NCI）已经针对一组60种人类癌细胞系筛选了60，000多种化合物，任何单个细胞系的50%生长抑制浓度（GI（50））只是细胞毒性或细胞抑制的指标，但60个这样的GI（50）值的模式编码了意想不到的丰富，关于药物作用机制和耐药性的详细信息。每种化合物的模式就像指纹一样，在数十亿种可区分的可能性中基本上是独一无二的。这些活性模式正在与测试药物的分子结构特征结合使用，以探索NCI超过460，000种化合物的数据库，并且它们正在提供对60种细胞系中潜在靶分子和活性调节剂的洞察，例如，该信息正在用于寻找活性不依赖于完整p53抑制基因功能的候选抗癌药物。这种信息密集型策略在产生新的临床活性药物方面的有效性还有待观察。
Since 1990, the National Cancer institute (NCI) has screened more than 60,000 compounds against a panel of 60 human cancer cell lines, The 50-percent growth-inhibitory concentration (GI(50)) for any single cell line is simply an index of cytotoxicity or cytostasis, but the patterns of 60 such GI(50) values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460,000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines, For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.