Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, Australia.
Trends Pharmacol Sci. 2019 Jul;40(7):506-516. doi: 10.1016/j.tips.2019.05.002. Epub 2019 May 31.
Drug development is a costly, time-consuming, and challenging endeavour, with only a few agents reaching the threshold of approval for clinical use. Therefore, approaches to more efficiently identify targets that are likely to translate to clinical benefit are required. Interrogation of the human genome in large patient cohorts has rapidly advanced our knowledge of the genetic architecture and underlying mechanisms of many diseases, including nonalcoholic fatty liver disease (NAFLD). There are no approved pharmacotherapies for NAFLD currently. Genetic insights provide a powerful and new approach to infer and prioritise candidate drugs, with such selection avoiding myriad pitfalls, while defining likely benefits. In this review, we discuss the prospects and challenges for the optimal utilisation of genetic findings for improving and accelerating the NAFLD drug discovery pipeline.
药物研发是一项昂贵、耗时且具有挑战性的工作，只有少数药物能达到临床应用批准的门槛。因此，需要采用更有效的方法来识别可能带来临床获益的靶点。对大量患者队列的人类基因组进行分析，使我们迅速了解了许多疾病（包括非酒精性脂肪性肝病 (NAFLD)）的遗传结构和潜在机制。目前，尚无针对 NAFLD 的批准药物疗法。遗传见解为推断和优先选择候选药物提供了一种强大且新颖的方法，这种选择避免了无数的陷阱，同时确定了可能的益处。在这篇综述中，我们讨论了如何优化利用遗传发现来改善和加速 NAFLD 药物发现管道的前景和挑战。
