二肽基肽酶1抑制剂brensocatib研究进展

Advances in the dipeptidyl peptidase 1 inhibitor brensocatib

摘要

brensocatib是一种高选择性、可逆性竞争性二肽基肽酶1(dipeptidyl peptidase 1,DPP1)抑制剂,于2025年8月12日获准用于治疗成人和12岁及以上青少年的非囊性纤维化支气管扩张症(non-cystic fibrosis bronchiectasis,NCFBE),是该治疗领域的一项重要进展。其通过抑制DPP1,减少中性粒细胞丝氨酸蛋白酶的活化,从而有效减轻中性粒细胞介导的炎症反应和组织损伤。临床研究显示,brensocatib可显著降低NCFBE患者的年化肺部恶化率,减少恶化患者比例,延长首次恶化时间,并且整体耐受性良好。本文旨在全面综述brensocatib的作用机制、药效学、药动学、药物相互作用、安全性评价、临床研究、不良反应与注意事项、特殊人群用药及其在其他疾病中的临床前研究,以保障用药安全。

Abstract

Brensocatib is a highly selective, reversible and competitive inhibitor of dipeptidyl peptidase 1 (DPP1), approved on August 12, 2025, for the treatment of non-cystic fibrosis bronchiectasis (NCFBE) in adults and adolescents aged 12 years and older, marking a significant advancement in this therapeutic area. By inhibiting DPP1, it reduces activation of neutrophil serine proteases, thereby effectively attenuating neutrophil-mediated inflammation and tissue damage. Clinical studies have shown that brensocatib significantly reduces the annualized rate of pulmonary exacerbations, decreases the proportion of patients experiencing exacerbations, prolongs the time to first exacerbation, and demonstrates a favorable tolerability profile in patients with NCFBE. This article provides a comprehensive review of brensocatib's mechanism of action, pharmacodynamics, pharmacokinetics, drug interactions, safety assessment, clinical studies, adverse reactions and precautions, use in special populations, and preclinical research in other diseases, to ensure medication safety.

关键词

brensocatib / 二肽基肽酶1 / 中性粒细胞丝氨酸蛋白酶 / 非囊性纤维化支气管扩张症

Key words

brensocatib / dipeptidyl peptidase 1 / neutrophil serine proteases / non-cystic fibrosis bronchiectasis

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