The effectiveness of β-lactam antibiotics is increasingly influenced by serine β-lactamases (SBLs) and metallo-β-lactamases (MBLs), which can hydrolyze β-lactam antibiotics. The development of effective β-lactamase inhibitors is an important direction to extend use of β-lactam antibiotics. Although six SBL inhibitors have been approved for clinical use, but no MBL inhibitors or MBL/SBL dual-action inhibitors are available so far. Broad-spectrum targeting clinically relevant MBLs and SBLs is currently desirable, while it is not easy to achieve such a purpose owing to structural and mechanistic differences between MBLs and SBLs. In this review, we summarized recent advances of inhibitor chemotypes targeting MBLs and SBLs and their inhibition mechanisms, particularly including lead discovery and structural optimization strategies, with the aim to provide useful information for future efforts to develop new MBL and SBL inhibitors.

β-内酰胺类抗生素的有效性越来越受丝氨酸β-内酰胺酶（SBLs）和金属-β-内酰胺酶（MBLs）的影响，它们可以水解β-内酰胺类抗生素。开发有效的β-内酰胺酶抑制剂是扩大β-内酰胺类抗生素应用的重要方向。虽然已有六种SBL抑制剂获批临床使用，但目前尚无MBL抑制剂或MBL/SBL双作用抑制剂上市。目前需要广谱靶向临床相关的 MBLs 和 SBLs，但由于 MBLs 和 SBLs 之间的结构和机制差异，实现这一目的并不容易。在这篇综述中，我们总结了针对 MBLs 和 SBLs 的抑制剂化学型的最新进展及其抑制机制，特别是包括先导发现和结构优化策略，