前藥開發中的高失敗率仍然是目前醫藥行業的巨大壓力。通過分析小分子候選藥物物理化學性質的關係，來減少有效性和安全性相關的失敗藥物數量，經過各個公司不同的數據表明，這樣的做法是不可行的。

發表於《自然評論:藥物發現》(Nature reviews. Drug discovery)2015年6月的一篇評論文章，對阿斯利康，禮來公司，葛蘭素史克和輝瑞公司的失敗候選藥物進行了整合和數據分析，文章再次肯定了，在化合物優化過程中，對候選藥物的物理化學性質進行控製，有利於確定候選藥物的質量，並且指出化合物的物理化學性質與臨床失敗之間的關係是由於藥物的安全問題。文章還表明，進一步控製物理化學性質不會對失敗率產生顯著的影響，這是必須要做的工作，能夠解決與安全性相關的失敗。目前跨公司合作將更多的關注這方麵。

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.