Noblejas-López María Del Mar, Tébar-García David, López-Rosa Raquel, Alcaraz-Sanabria Ana, Cristóbal-Cueto Pablo, Pinedo-Serrano Alejandro, Rivas-García Lorenzo, Galán-Moya Eva M
Centro Regional de Investigaciones Biomédicas (CRIB), Campus de Albacete, Universidad de Castilla-La Mancha, 02008 Albacete, Spain.
Unidad de Investigación, Complejo Hospitalario Universitario de Albacete, 02008 Albacete, Spain.
Pharmaceutics. 2023 Oct 10;15(10):2442. doi: 10.3390/pharmaceutics15102442.
Targeted protein degradation has emerged as an alternative therapy against cancer, offering several advantages over traditional inhibitors. The new degrader drugs provide different therapeutic strategies: they could cross the phospholipid bilayer membrane by the addition of specific moieties to extracellular proteins. On the other hand, they could efficiently improve the degradation process by the generation of a ternary complex structure of an E3 ligase. Herein, we review the current trends in the use of TAC-based technologies (TACnologies), such as PROteolysis TArgeting Chimeras (PROTAC), PHOtochemically TArgeting Chimeras (PHOTAC), CLIck-formed Proteolysis TArgeting Chimeras (CLIPTAC), AUtophagy TArgeting Chimeras (AUTAC), AuTophagosome TEthering Compounds (ATTEC), LYsosome-TArgeting Chimeras (LYTAC), and DeUBiquitinase TArgeting Chimeras (DUBTAC), in experimental development and their progress towards clinical applications.
靶向蛋白降解已成为一种抗癌替代疗法，与传统抑制剂相比具有多个优势。新型降解剂药物提供了不同的治疗策略：通过向细胞外蛋白添加特定基团，它们可以穿过磷脂双分子层膜。另一方面，它们可以通过生成E3连接酶的三元复合物结构来有效改善降解过程。在此，我们综述了基于TAC的技术（TAC技术）的当前应用趋势，例如蛋白酶靶向嵌合体（PROTAC）、光化学靶向嵌合体（PHOTAC）、点击形成的蛋白酶靶向嵌合体（CLIPTAC）、自噬靶向嵌合体（AUTAC）、自噬体连接化合物（ATTEC）、溶酶体靶向嵌合体（LYTAC）和去泛素酶靶向嵌合体（DUBTAC）在实验开发中的情况以及它们在临床应用方面的进展。
