Haridas V, Dutta Souvik, Munjal Akshay, Singh Shailja
Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.
Department of Chemistry, Indian Institute of Technology Palakkad, Palakkad, Kerala 678623, India.
iScience. 2024 Mar 26;27(5):109574. doi: 10.1016/j.isci.2024.109574. eCollection 2024 May 17.
The chemical understanding of biological processes provides not only a deeper insight but also a solution to abnormal biological functioning. Protein degradation, a natural biological process for debris removal in the cell, has been studied for years. The recent finding that natural degradation pathways can be utilized for therapeutic purposes is a paradigm shift in the drug discovery approach. Methods such as Proteolysis Targeting Chimera (PROTAC), lysosomal targeting chimera, hydrophobic tagging, AUtophagy TArgeting Chimera, AUTOphagy TArgeting Chimera and several other variants of these methods have made a considerable impact on the way of drug design. Few selected examples testify that a huge wave of change is on the way. The drug design based on the targeted protein degradation is a powerful tool in our arsenal. More molecules will be invented that will uncover the hidden secrets of biological functioning and provide enduring solutions to several unmet medical needs.
对生物过程的化学理解不仅能提供更深入的见解，还能为异常的生物功能提供解决方案。蛋白质降解作为细胞内清除碎片的自然生物过程，已被研究多年。最近发现自然降解途径可用于治疗目的，这是药物发现方法的一个范式转变。诸如蛋白酶靶向嵌合体（PROTAC）、溶酶体靶向嵌合体、疏水标记、自噬靶向嵌合体、自噬靶向嵌合体以及这些方法的其他几种变体等方法，已对药物设计方式产生了重大影响。少数精选的例子证明，一场巨大的变革浪潮即将到来。基于靶向蛋白质降解的药物设计是我们武器库中的一个强大工具。将会发明更多的分子，这些分子将揭开生物功能的隐藏秘密，并为一些未满足的医疗需求提供持久的解决方案。
