Placidi Giampaolo, Mattu Clara, Ciardelli Gianluca, Campa Carlo C
Italian Institute for Genomic Medicine, Candiolo, Italy.
Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
Front Cell Dev Biol. 2023 Mar 10;11:1125801. doi: 10.3389/fcell.2023.1125801. eCollection 2023.
Over the past years a growing number of studies highlighted the pivotal role of intracellular trafficking in cell physiology. Among the distinct transport itineraries connecting the endocytic system, both internalization (endocytosis) and recycling (endocytic recycling) pathways were found fundamental to ensure cellular sensing, cell-to-cell communication, cellular division, and collective cell migration in tissue specific-contexts. Consistently, the dysregulation of endocytic trafficking pathways is correlated with several human diseases including both cancers and neurodegeneration. Aimed at suppress specific intracellular trafficking routes involved in disease onset and progression, huge efforts have been made to identify small molecule inhibitors with suitable pharmacological properties for administration. Here, we review most used drugs and recently discovered small molecules able to block endocytosis and endocytic recycling pathways. We characterize such pharmacological inhibitors by emphasizing their target specificity, molecular affinity, biological activity and efficacy in both and experimental models.
在过去几年中,越来越多的研究强调了细胞内运输在细胞生理学中的关键作用。在连接内吞系统的不同运输途径中,内化(内吞作用)和回收(内吞回收)途径对于确保细胞感知、细胞间通讯、细胞分裂以及组织特定环境中的集体细胞迁移都至关重要。同样,内吞运输途径的失调与包括癌症和神经退行性疾病在内的多种人类疾病相关。为了抑制参与疾病发生和发展的特定细胞内运输途径,人们付出了巨大努力来寻找具有合适药理特性以便给药的小分子抑制剂。在此,我们综述了最常用的药物以及最近发现的能够阻断内吞作用和内吞回收途径的小分子。我们通过强调它们在体外和体内实验模型中的靶标特异性、分子亲和力、生物活性和功效来表征这些药理抑制剂。