Schlyer Sabine, Horuk Richard
Department of Computational Chemistry, Berlex Biosciences, Richmond, CA 94804, USA.
Drug Discov Today. 2006 Jun;11(11-12):481-93. doi: 10.1016/j.drudis.2006.04.008.
Huey Lewis and the News summed it up nicely in their 1980s hit record: 'I want a new drug, one that won't make me sick, one that won't make me crash my car, or make me feel three feet thick'. The song could be an anthem for drug discovery in the pharmaceutical industry. We all want new and better drugs with fewer side effects, which are effective for combating the major diseases of our time: cancer, heart disease, obesity and autoimmune diseases. How do we get these new drugs? There are currently some new ideas in drug discovery, centered on that staple diet of the pharmaceutical industry, the G-protein-coupled receptor (GPCR) superfamily. In silico methods, employing receptor-based modeling, offer a more rational approach in the design of drugs targeting GPCRs. These approaches can be used to understand receptor selectivity and species specificity of drugs that interact with GPCRs. In addition, there are various novel approaches, such as the design and potential utility of drugs that target more than one GPCR ('dual specificity' drugs).
休伊·刘易斯与新闻合唱团在他们20世纪80年代的热门唱片中说得很好:“我想要一种新药,一种不会让我生病的药,一种不会让我撞车,也不会让我感觉迟钝的药”。这首歌可以成为制药行业药物研发的颂歌。我们都想要副作用更少、能有效对抗当今主要疾病(癌症、心脏病、肥胖症和自身免疫性疾病)的更新更好的药物。我们如何获得这些新药呢?目前在药物研发方面有一些新思路,其核心是制药行业的主要研究对象——G蛋白偶联受体(GPCR)超家族。采用基于受体建模的计算机模拟方法,为设计针对GPCR的药物提供了一种更合理的途径。这些方法可用于理解与GPCR相互作用的药物的受体选择性和物种特异性。此外,还有各种新颖的方法,例如针对一种以上GPCR的药物(“双特异性”药物)的设计和潜在用途。