The reactive functionalities of drugs that engage in covalent interactions with the enzyme/receptor residue in either a reversible or an irreversible manner are called 'warheads'. Covalent warheads that were previously neglected because of safety concerns have recently gained center stage as a result of their various advantages over noncovalent drugs, including increased selectivity, increased residence time, and higher potency. With the approval of several covalent inhibitors over the past decade, research in this area has accelerated. Various strategies are being continuously developed to tune the characteristics of warheads to improve their potency and mitigate toxicity. Here, we review research progress in warhead discovery over the past 5 years to provide valuable insights for future drug discovery.

以可逆或不可逆的方式与酶/受体残基发生共价相互作用的药物的反应功能被称为“弹头”。以前因安全问题而被忽视的共价弹头最近因其相对于非共价药物的各种优势而获得了关注，包括更高的选择性、更长的停留时间和更高的效力。随着过去十年中几种共价抑制剂的批准，该领域的研究加速了。人们正在不断开发各种策略来调整弹头的特性，以提高其效力并减轻毒性。在这里，我们回顾过去5年弹头发现的研究进展，为未来的药物发现提供有价值的见解。