Eskitis Institute, Griffith University, Brisbane, Queensland 4111, Australia.
Chem Biodivers. 2013 Apr;10(4):524-37. doi: 10.1002/cbdv.201200302.
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.
在 1981 年 1 月至 2010 年 12 月期间，有 1068 种小分子新化学实体（NCEs）被引入，其中约 34%是天然产物或其类似物。虽然这一指标反映了天然产物在为制药行业提供新的化学起点（先导化合物）方面所发挥的作用，但它并没有捕捉到过去 20 年来这种方法的衰落，因为高通量筛选（HTS）的纯化合物库变得越来越流行。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，无法预先加载提取物或馏分的化学成分，使其符合先导化合物和药物样化学空间的要求。为了解决这一不平衡，已经开发了一种基于亲脂性的方法，用 clog P 来衡量，再加上在分离和结构阐明方面的进展，就可以在与纯化合物筛选兼容的时间框架内提供天然产物先导化合物。
