嵌合体(遗传学)
溶酶体
细胞生物学
计算生物学
化学
纳米技术
生物
生物化学
材料科学
基因
酶
作者
Jinpeng Wang,Yuechen Wang,Fenfang Yang,Qinhong Luo,Qinhong Luo,Zhanjun Hou,Yan Xing,Fei Lu,Zigang Li,Zigang Li,Feng Yin,Feng Yin
标识
DOI:10.1021/acschembio.4c00092
摘要
Targeted protein degradation is becoming more and more important in the field of drug development. Compared with proteasomal-based degraders, lysosomal-based degraders have a broader target spectrum of targets, which have been demonstrated to have great potential, especially in degrading undruggable proteins. Recently, we developed a programmable and facile screening PROTAC development platform based on peptide self-assembly termed split-and-mix PROTAC (SM-PROTAC). In this study, we applied this technology for the development of lysosome-based degraders, named a split-and-mix chaperone-mediated autophagy-based degrader (SM-CMAD). We successfully demonstrated SM-CMAD as a universal platform by degrading several targets, including ERα, AR, MEK1/2, and BCR-ABL. Different from other lysosomal-based degraders, SM-CMAD was capable of facile screening with programmable ligand ratios. We believe that our work will promote the development of other multifunctional molecules and clinical translation for lysosomal-based degraders.
科研通智能强力驱动
Strongly Powered by AbleSci AI