Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, Shandong, China.
The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao University, Qingdao 266071, Shandong, China.
Int J Biol Macromol. 2024 Mar;261(Pt 2):129864. doi: 10.1016/j.ijbiomac.2024.129864. Epub 2024 Jan 30.
Proteolysis targeting chimera (PROTAC) technology is a promising new mode of targeted protein degradation with significant transformative implications for the clinical treatment of different diseases. Nevertheless, while this technology offers numerous advantages, on-target off-tumour toxicity in healthy cells remains a major challenge for clinical application in cancer therapy. Strategies are presently being explored to optimize degradation activity with cellular selectivity to minimize undesirable side effects. PROTAC-antibody conjugates and PROTAC-aptamer conjugates are unique innovations that combine PROTACs and biomacromolecules. These novel PROTAC-biomacromolecule conjugates (PBCs) can enhance the targetability of PROTACs and reduce their off-target side-effects. The combination of potent PROTACs and highly safe biomacromolecules will pioneer an emerging trend in targeted protein degradation. In our review, we have summarized recent advances in PBCs, discussed current challenges, and outlooked opportunities for future research in the field.
蛋白水解靶向嵌合体（PROTAC）技术是一种有前途的靶向蛋白降解新模式，对不同疾病的临床治疗具有重大变革意义。然而，尽管这项技术有许多优势，但在肿瘤治疗的临床应用中，健康细胞的靶外肿瘤毒性仍然是一个主要挑战。目前正在探索策略，以优化具有细胞选择性的降解活性，最大限度地减少不良副作用。PROTAC-抗体缀合物和 PROTAC-适体缀合物是独特的创新，将 PROTAC 和生物大分子结合在一起。这些新型 PROTAC-生物大分子缀合物（PBC）可以增强 PROTAC 的靶向性并降低其脱靶副作用。将强效 PROTAC 和高度安全的生物大分子结合起来，将开创靶向蛋白降解的新兴趋势。在我们的综述中，我们总结了 PBC 的最新进展，讨论了当前的挑战，并展望了该领域未来研究的机会。
