Front-Loading Natural-Product-Screening Libraries for log P: Background, Development, and Implementation
Front-Loading Natural-Product-Screening Libraries for log P: Background, Development, and Implementation
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DOI：
10.1002/cbdv.201200302
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发表时间：
2013-04-01
影响因子：
2.9
通讯作者：
Quinn, Ronald J.
中科院分区：
文献类型：
--
作者：
Camp, David;Campitelli, Marc;Quinn, Ronald J.
从1981年1月到2010年12月，共发现1068种小分子新化学实体（NCEs），其中约34%是天然产物或类似物。虽然这一指标反映了天然产品在为制药行业提供新的化学起点（先导）方面所发挥的影响，但它并没有反映出这种方法在过去20年里随着纯化合物文库的高通量筛选（HTS）变得越来越流行而遭受的衰退。在HTS范式中，天然产物药物发现的一个障碍是缺乏明确的策略，无法预先装载提取物或部分的化学成分，使其符合铅和药物样的化学空间。为了解决这种不平衡，一种基于亲脂性（clog P测量）的方法已经开发出来，再加上在分离和结构解析方面取得的进展，可以在与纯化合物筛选相容的时间线上提供天然产物先导。
In the period from January 1981 to December 2010, 1068 small-molecule new chemical entities (NCEs) were introduced, of which ca. 34% are either a natural product or a close analogue. While this metric reflects the impact natural products have played in delivering new chemical starting points (leads) for the pharmaceutical industry, it does not capture the decline this approach has suffered over the last 20 years as the high-throughput screening (HTS) of pure compound libraries has become more popular. An impediment to natural-product drug discovery in the HTS paradigm is the lack of a clear strategy that enables front-loading of an extract or fraction's chemical constituents so that they are compliant with lead- and drug-like chemical space. To address this imbalance, an approach based on lipophilicity, as measured by clog P has been developed that, together with advances being made in isolation and structural elucidation, can afford natural product leads in timelines compatible with pure compound screening.