State Key Laboratory of Drug Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Adv Exp Med Biol. 2019;1163:1-23. doi: 10.1007/978-981-13-8719-7_1.
Allosteric regulation is a ubiquitous strategy employed in nature to control cellular processes by regulating the affinities of biomolecules. Allosteric modulators are able to tune the protein/substrate affinity in a highly predictable way, suggesting that such modulators may represent safe drugs. Tremendous advances have been made in the development of allosteric modulators and the characterization of their therapeutic targets. Here, we briefly introduce several representative allosteric modulators of important drug targets, such as the G protein-coupled receptor family. We also review the state-of-the-art experimental and computational approaches used in allosteric drug development. The accumulated knowledge of allosteric regulation and the technical progress made in drug development will lead to an explosion of promising allosteric drugs in the near future.
变构调节是自然界中一种普遍存在的策略，通过调节生物分子的亲和力来控制细胞过程。变构调节剂能够以高度可预测的方式调节蛋白质/底物的亲和力，这表明此类调节剂可能代表安全的药物。在变构调节剂的开发和治疗靶点的表征方面已经取得了巨大的进展。在这里，我们简要介绍了几种重要药物靶点的代表性变构调节剂，如 G 蛋白偶联受体家族。我们还回顾了变构药物开发中使用的最新实验和计算方法。变构调节的积累知识和药物开发方面的技术进步将在不久的将来带来大量有前途的变构药物。
