Yang Bo, Wang Wen-Jing, Li Lin-Li
Yao Xue Xue Bao. 2014 Feb;49(2):158-65.
Small molecule covalent inhibitors, or called as irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity. Nevertheless, these agents may also exhibit larger toxicity once off-target effects arise. This "double-edged swords" property often leads drug researchers to avoid attaching them. In recent years, some problems such as drug resistance are difficult to be solved with reversible inhibitors leading researchers to pay more attention on the covalent inhibitors. In this review, we shall make a short summary to the recent research progress of covalent inhibitors and the interaction modes between covalent inhibitors and their target protein residues.
小分子共价抑制剂，也被称为不可逆抑制剂，是一类通过共价键与靶点不可逆结合来发挥其生物学功能的抑制剂。与非共价抑制剂相比，共价抑制剂在生物活性方面具有明显优势。然而，一旦出现脱靶效应，这些药物也可能表现出更大的毒性。这种“双刃剑”特性常常导致药物研究人员对其避而远之。近年来，诸如耐药性等一些问题难以用可逆抑制剂解决，这使得研究人员更加关注共价抑制剂。在本综述中，我们将对共价抑制剂的最新研究进展以及共价抑制剂与其靶蛋白残基之间的相互作用模式做一个简要总结。
