Chemical Society Reviews cover review Lu Boxun / Ding Lu / Fei Yiyan / Xing Dong co-published a review of new technologies for degradation of lysosomal pathways represented by ATTEC and other technologies

Chemical Society Reviews cover roundup

Lu Boxun / Ding Lu / Fei Yiyan / Xing Dong collaborated to publish a review of new degradation technologies targeting lysosomal pathways represented by ATTEC and other technologies

This paper was published as the cover paper of the journal Chemical Society Reviews, Issue 21, 2022

Summary of major technologies targeting lysosomal degradation pathways

On October 31, 2022, Lu Boxun/Ding Lu, School of Life Sciences, Fudan University, Fei Yiyan, School of Information Science and Engineering, and Xing Dong, School of Chemical and Molecular Engineering, East China Normal University, collaborated at Chemical The journal Society Reviews (IF=60.
615) published a cover paper titled "Emerging degrader technologies engaging lysosomal pathways.
" (New Degradation Technologies Targeting Lysosomal Pathways).

In the past two decades, proteasome-based degradation technologies such as PROTAC have developed rapidly, but there are still significant limitations
.
In the past three years, a number of advances have been made in the field of targeted degradation based on autophagy-lysosomes and endosome-lysosomes, and a new field of degradation technology independent of PROTAC and proteasome has been established
。 As the inventor of one of the representative technologies ATTEC, the author of this paper was invited to write this review, comprehensively and systematically summarize the important R&D progress in this field from chemistry and biology, analyze the core keys to the development and design of such technologies, and look forward to future research in this field to promote ATTEC and other emerging lysosomal targeted degradation technologies provide unique insights
.

This 45-page, 34,000-word paper, divided into 8 chapters, systematically discusses autophagy-based degradation techniques (ATTEC, AUTAC and AUTOTAC), and endosome-lysosomal pathway degradation technologies (LYTAC and MoDE-A The background, principle and case, the mechanism of action and verification methods of lysosomal pathway degraders, the selection strategies of various technical targets, the identification or design of strategies targeting lysosomal pathway degraders, and the potential advantages and limitations
of various types of lysosomal pathway degraders.
This paper is detailed and rich in content, which is convenient for readers to systematically understand the basic principles, existing cases, development directions and urgent problems
of lysosomal targeted degradation technology.

In 2019, a collaborative team composed of Lu Boxun, Ding Li, Fei Yiyan and others published in Nature a targeted degradation technology for biomacromolecules targeting autophagy-lysosomes (ATTEC, AuTophagy-TEthering Compounds), the related field has given high praise to this research, recommended by many authoritative journals, Nature also issued special reviews in the same period, and then this paper was selected by Nature Top 10 Outstanding Scientific and Technical Papers
of 2019.
In 2021, the collaborative team published the targeted degradation technology of lipid droplets in the form of a cover paper at Cell Research, reporting the targeted degradation
of non-protein biological macromolecules for the first time.
Since then, a number of domestic and foreign research teams have developed targeted degradation molecules based on ATTEC principles, or other new technologies
targeting lysosomes.
This review paper systematically summarizes and deeply analyzes the representative technologies in this field, and provides insights for the further development of the field, hoping that related technologies can have more vigorous development in the near future, and help biomedical development, original drug research and development and improve people's health through innovative technical means
.

Doi: 10.
1039/d2cs00624c

Original link: https://pubs.
rsc.
org/en/content/articlelanding/2022/cs/d2cs00624c