Drug Discovery Unit, College of Life Sciences, University of Dundee, UK.
Curr Top Med Chem. 2011;11(10):1275-83. doi: 10.2174/156802611795429185.
The discovery of drugs is a lengthy, high-risk and expensive business taking at least 12 years and is estimated to cost upwards of US$800 million for each drug to be successfully approved for clinical use. Much of this cost is driven by the late phase clinical trials and therefore the ability to terminate early those projects destined to fail is paramount to prevent unwanted costs and wasted effort. Although neglected diseases drug discovery is driven more by unmet medical need rather than financial considerations, the need to minimise wasted money and resources is even more vital in this under-funded area. To ensure any drug discovery project is addressing the requirements of the patients and health care providers and delivering a benefit over existing therapies, the ideal attributes of a novel drug needs to be pre-defined by a set of criteria called a target product profile. Using a target product profile the drug discovery process, clinical study design, and compound characteristics can be defined all the way back through to the suitability or druggability of the intended biochemical target. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success.
药物发现是一项漫长、高风险且昂贵的业务,至少需要 12 年的时间,并且每一种药物要成功获得临床批准,估计成本超过 8 亿美元。其中大部分成本是由后期临床试验驱动的,因此尽早终止那些注定要失败的项目对于防止不必要的成本和浪费的努力至关重要。尽管治疗罕见病的药物发现更多地是由未满足的医疗需求驱动,而不是经济考虑,但在这个资金不足的领域,尽量减少资金和资源的浪费甚至更为重要。为了确保任何药物发现项目都能满足患者和医疗保健提供者的需求,并提供优于现有治疗方法的益处,需要通过一套称为目标产品概况的标准来预先定义新药的理想属性。使用目标产品概况,可以从一开始就定义药物发现过程、临床研究设计和化合物特性,一直到预期生化靶标的适用性或成药性。评估和优先考虑最有希望进入筛选计划的靶点对于最大限度地提高成功机会至关重要。