Since the discovery of the key role of cathepsin K in bone resorption, cysteine cathepsins have been investigated by pharmaceutical companies as drug targets. The first clinical results from targeting cathepsins by activity-based probes and substrates are paving the way for the next generation of molecular diagnostic imaging, whereas the majority of antibody–drug conjugates currently in clinical trials depend on activation by cathepsins. Finally, cathepsins have emerged as suitable vehicles for targeted drug delivery. It is therefore timely to review the future of cathepsins in drug discovery. We focus here on inflammation-associated diseases because dysregulation of the immune system accompanied by elevated cathepsin activity is a common feature of these conditions.

自发现组织蛋白酶K在骨吸收中的关键作用以来，半胱氨酸组织蛋白酶已被制药公司研究为药物靶标。通过基于活性的探针和底物靶向组织蛋白酶的首批临床结果为下一代分子诊断成像铺平了道路，而目前临床试验中的大多数抗体-药物偶联物都依赖于组织蛋白酶的激活。最后，组织蛋白酶已成为用于靶向药物递送的合适载体。因此，现在有必要回顾组织蛋白酶在药物发现中的未来。我们将重点放在与炎症相关的疾病上，因为免疫系统失调伴随组织蛋白酶活性升高是这些疾病的共同特征。