Chiesi M, Huppertz C, Hofbauer K G
Cardiovascular and Metabolic Diseases Research, Novartis Pharma AG, CH 4002 Basel, Switzerland.
Trends Pharmacol Sci. 2001 May;22(5):247-54. doi: 10.1016/s0165-6147(00)01664-3.
The search for anti-obesity agents has become one of the most exciting areas in drug discovery. Subsequent to an enormous increase in the number of possible molecular targets, the focus has shifted from target identification to target validation. Because important biological functions such as the regulation of energy intake and expenditure are controlled by complex systems, an improved understanding of pathophysiology is a prerequisite for the selection of successful development candidates for the treatment of obesity. Although most of the information on the regulation of energy balance has been obtained from rodents, various monogenic forms of human obesity provide clinical proof of concept for some of these mechanisms. However, it is still not known which are the most promising clinical approaches to lowering body weight and subsequently reducing morbidity and mortality.
寻找抗肥胖药物已成为药物研发中最令人兴奋的领域之一。在可能的分子靶点数量大幅增加之后，重点已从靶点识别转向靶点验证。由于能量摄入和消耗的调节等重要生物学功能是由复杂系统控制的，因此更好地理解病理生理学是选择成功的肥胖治疗开发候选药物的先决条件。尽管关于能量平衡调节的大多数信息是从啮齿动物获得的，但人类肥胖的各种单基因形式为其中一些机制提供了临床概念验证。然而，目前仍不清楚哪些是降低体重并随后降低发病率和死亡率最有前景的临床方法。
