前药开发中的高失败率仍然是目前医药行业的巨大压力。通过分析小分子候选药物物理化学性质的关系，来减少有效性和安全性相关的失败药物数量，经过各个公司不同的数据表明，这样的做法是不可行的。

        发表于《自然评论:药物发现》(Nature reviews. Drug discovery)2015年6月的一篇评论文章，对阿斯利康，礼来公司，葛兰素史克和辉瑞公司的失败候选药物进行了整合和数据分析，文章再次肯定了，在化合物优化过程中，对候选药物的物理化学性质进行控制，有利于确定候选药物的质量，并且指出化合物的物理化学性质与临床失败之间的关系是由于药物的安全问题。文章还表明，进一步控制物理化学性质不会对失败率产生显著的影响，这是必须要做的工作，能够解决与安全性相关的失败。目前跨公司合作将更多的关注这方面。

        原文摘要：

        An analysis of the attrition of drug candidates from four major pharmaceutical companies.

        Waring MJ1, Arrowsmith J2, Leach AR3, Leeson PD4, Mandrell S2, Owen RM5, Pairaudeau G1, Pennie WD6, Pickett SD3, Wang J7, Wallace O8, Weir A2.

        The pharmaceutical industry remains under huge pressure to address the high attrition rates indrug development. Attempts to reduce the number of efficacy- and safety-related failures by analysing possible links to the physicochemical properties of small-molecule drug candidates have been inconclusive because of the limited size of data sets from individual companies. Here, we describe the compilation and analysis of combined data on the attrition of drug candidates from AstraZeneca, Eli Lilly and Company, GlaxoSmithKline and Pfizer. The analysis reaffirms that control of physicochemical properties during compound optimization is beneficial in identifying compounds of candidate drug quality and indicates for the first time a link between the physicochemical properties of compounds and clinical failure due to safety issues. The results also suggest that further control of physicochemical properties is unlikely to have a significant effect on attrition rates and that additional work is required to address safety-related failures. Further cross-company collaborations will be crucial to future progress in this area.