Division of Andrology, Sexual Medicine Unit, Mansoura Faculty of Medicine, Mansoura, Egypt.
Expert Opin Ther Targets. 2011 Mar;15(3):325-40. doi: 10.1517/14728222.2011.551008. Epub 2011 Jan 5.
The ratio between research and successful targets in a disease class gives a good indication about the extent of the exploration of additional targets for diseases in that class. This ratio is still very low for the field of sexual medicine. 'Failures' in drug development can be highly instructive, but are not often addressed.
We performed a review of the literature based on published data on four failure stories including targeting adrenergic receptors for erectile dysfunction (ED), targeting dopamine receptors by apomorphine for ED, serotonergic transporters as a target for premature ejaculation and PDE5 as a target for female sexual dysfunctions. The search included: i) a MEDLINE search from 1966 through November 2010 limited to English language medical literature, ii) relevant abstracts from 2009 and 2010 and iii) a pipeline search for therapeutics in development. The aim is to inform readers about the lessons learned from four selected failed therapeutic stories during therapeutic target exploration for sexual dysfunctions.
By learning from failures, a drug may not only be kept alive, but also better therapeutic strategies and design of new drugs may be developed.
疾病领域中研究与成功靶点的比例可以很好地反映该疾病领域中对其他靶点的探索程度。性医学领域的这一比例仍然非常低。药物开发中的“失败”可以提供非常有价值的经验教训,但往往未被重视。
我们根据有关四个失败案例的已发表数据,对文献进行了回顾,这些案例包括针对勃起功能障碍(ED)的肾上腺素能受体、阿扑吗啡针对 ED 的多巴胺受体、作为早泄靶点的 5-羟色胺转运体以及作为女性性功能障碍靶点的 PDE5。搜索范围包括:i)限定于英语医学文献的 1966 年至 2010 年 11 月 MEDLINE 搜索,ii)2009 年和 2010 年的相关摘要,以及 iii)正在开发的治疗方法的管线搜索。目的是让读者了解在治疗性功能障碍的治疗靶点探索过程中,从四个选定的失败治疗案例中吸取的经验教训。
通过从失败中吸取教训,不仅可以保留药物,还可以开发出更好的治疗策略和新型药物设计。