蛋白质-蛋白质相互作用（PPI）是许多生物过程的基础，在多种疾病的发生和发展中发挥着重要作用。针对肿瘤相关蛋白与新兴小分子药物之间的相互作用已成为治疗人类疾病，尤其是肿瘤的一种有吸引力的方法。令人鼓舞的是，基于 PPI 的选择性治疗剂在过去十年中迅速发展，为癌症患者的新疗法提供了有希望的前景。本文从多个方面全面阐述了质子泵抑制剂小分子调节剂的发现和发展，重点关注质子泵抑制剂在疾病中的作用、药物设计与发现策略、构效关系、内在困境以及未来发展方向。© 2023 中国药学会中国医学科学院药物研究所.由 Elsevier B.V. 制作和主持

Protein-protein interactions (PPIs) are fundamental to many biological processes that play an important role in the occurrence and development of a variety of diseases. Targeting the interaction between tumour-related proteins with emerging small molecule drugs has become an attractive approach for treatment of human diseases, especially tumours. Encouragingly, selective PPI-based therapeutic agents have been rapidly advancing over the past decade, providing promising perspectives for novel therapies for patients with cancer. In this review we comprehensively clarify the discovery and development of small molecule modulators of PPIs from multiple aspects, focusing on PPIs in disease, drug design and discovery strategies, structure-activity relationships, inherent dilemmas, and future directions.© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.