Serine proteases play critical roles in many physiological and pathological processes, and are proven diagnostic and therapeutic targets in a number of clinical indications. Suppression of the aberrant proteolytic activities of these proteases has been clinically used for the treatments of relevant diseases. Polypeptides with 10-20 residues are of great interests as medicinal modulators of serine proteases, because these peptides demonstrate the characteristics of both small molecule drugs and macromolecular drugs. In this review, we summarized the recent development of peptide-based inhibitors against serine proteases with potent inhibitory and high specificity comparable to monoclonal antibodies. In addition, we also discussed the strategies of enhancing plasma half-life and bioavailability of peptides in vivo, which is the main hurdle that limits the clinical translation of peptide-based drugs. This review advocates new avenue for the development of effective serine protease inhibitors and highlights the prospect of the medicinal use of these inhibitors.

丝氨酸蛋白酶在许多生理和病理过程中起着关键作用，并且在许多临床适应症中被证明是诊断和治疗靶标。这些蛋白酶的异常蛋白水解活性的抑制已在临床上用于治疗相关疾病。具有10-20个残基的多肽作为丝氨酸蛋白酶的药物调节剂具有极大的兴趣，因为这些肽表现出小分子药物和大分子药物的特征。在这篇综述中，我们总结了基于肽的针对丝氨酸蛋白酶的抑制剂的最新进展，该抑制剂具有与单克隆抗体相当的强抑制性和高特异性。此外，我们还讨论了提高体内血浆半衰期和提高多肽生物利用度的策略，这是限制基于肽的药物临床翻译的主要障碍。这篇评论提倡开发有效的丝氨酸蛋白酶抑制剂的新途径，并强调了这些抑制剂的药用前景。