Hanson J
Laboratoire de Pharmacologie moléculaire, GIGA - Molecular Biology of Diseases, ULiège, Belgique.
Laboratoire de Chimie pharmaceutique, CIRM, Liège, Belgique.
Rev Med Liege. 2020 May;75(5-6):460-465.
A therapeutic target can be defined as the biochemical entity by which a drug exerts its beneficial effects. Historically, most drugs have been used without a precise knowledge of their mechanism of action. The rational drug design for a predefined target has been progressively implemented during the second half of the 20th century. Recent advances in genomics have accelerated the discovery of several targets involved in many pathologies. During the recent period, there has also been a diversification of the types of targets used in therapy. Generally, the proteins modulated by drugs belonged mainly to the families of membrane receptors (receptors coupled to G proteins, ion channels, etc.), nuclear receptors or enzymes. Technological advances in the field of therapeutic antibodies and biotechnologies enabled curative agents to reach previously undruggable targets. In this article, we review these trends and illustrate them by various examples, notably in the field of anticancer drugs, lipid-lowering drugs, gene therapy or antisense therapy.
治疗靶点可定义为药物发挥有益作用所作用的生化实体。从历史上看，大多数药物在使用时对其作用机制并无精确了解。针对预定义靶点的合理药物设计在20世纪下半叶逐步得到应用。基因组学的最新进展加速了对许多疾病所涉及的多个靶点的发现。近年来，治疗中使用的靶点类型也出现了多样化。一般来说，药物调节的蛋白质主要属于膜受体家族（与G蛋白偶联的受体、离子通道等）、核受体或酶。治疗性抗体和生物技术领域的技术进步使治疗药物能够作用于以前难以成药的靶点。在本文中，我们回顾这些趋势，并通过各种实例进行说明，特别是在抗癌药物、降脂药物、基因治疗或反义治疗领域。
