Avanesian Agnesa, Semnani Sahar, Jafari Mahtab
Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697, USA.
Drug Discov Today. 2009 Aug;14(15-16):761-6. doi: 10.1016/j.drudis.2009.05.010. Epub 2009 May 29.
Once a molecule is identified as a potential drug, the detection of adverse drug reactions is one of the key components of its development and the FDA approval process. We propose using Drosophila melanogaster to screen for reproductive adverse drug reactions in the early stages of drug development. Compared with other non-mammalian models, D. melanogaster has many similarities to the mammalian reproductive system, including putative sex hormones and conserved proteins involved in genitourinary development. Furthermore, the D. melanogaster model would present significant advantages in time efficiency and cost-effectiveness compared with mammalian models. We present data on methotrexate (MTX) reproductive adverse events in multiple animal models, including fruit flies, as proof-of-concept for the use of the D. melanogaster model.
一旦一种分子被确定为潜在药物,药物不良反应的检测就是其研发以及美国食品药品监督管理局(FDA)审批过程的关键组成部分之一。我们建议在药物研发的早期阶段使用黑腹果蝇来筛选生殖方面的药物不良反应。与其他非哺乳动物模型相比,黑腹果蝇与哺乳动物的生殖系统有许多相似之处,包括假定的性激素以及参与泌尿生殖系统发育的保守蛋白。此外,与哺乳动物模型相比,黑腹果蝇模型在时间效率和成本效益方面具有显著优势。我们展示了包括果蝇在内的多种动物模型中关于甲氨蝶呤(MTX)生殖不良事件的数据,以此作为使用黑腹果蝇模型的概念验证。