目标临床疗效的计算机预测

Christina M. Friedrich, Thomas S. Paterson
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引用次数: 15

摘要

随着技术进步彻底改变了药物发现中新靶点识别的过程,验证越来越多的靶点与预测的人类临床疗效的问题正在形成瓶颈。所有的新靶标鉴定方法都依赖于部分和孤立的人类疾病模型。例如,诸如差异基因表达(比较几个患病和健康患者中特定基因的上调)和高通量化合物筛选(识别被认为与疾病过程有关的途径的化合物)等方法都是重要的研究,它们揭示了靶标与特定疾病过程的关系,但这种“暗示”缺乏预测靶标临床疗效的特异性。鉴于目前的靶标识别方法不能完美地预测临床疗效,而且从成本和时间的角度来看,将所有靶标推进到开发阶段是令人望而却步的——如何在新靶标之间做出理性的选择呢?
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In silico predictions of target clinical efficacy

As technological advances revolutionize the process of novel target identification in drug discovery, the problem of validating this ever-growing number of targets against predicted clinical efficacy in humans is creating a bottleneck. All methods of novel target identification rely on partial and isolated models of human disease. For example, methods such as differential gene expression (comparing the upregulation of a particular gene in several sick versus healthy patients) and high-throughput compound screening (identifying compounds that hit a pathway that is thought to be involved in a disease process) are important research that intimate target involvement in a particular disease process, but such ‘hints’ lack specificity for predicting the clinical efficacy of a target. Given that current target identification methods are an imperfect predictor of clinical efficacy and that moving all targets forward through to development is prohibitive in terms of cost and time - how can rational choices between novel targets be made?

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