Protein degradation targets the chimera database PROTAC-DB 2.0

       Proteolytic targeting chimera (PROTAC) is an emerging drug therapy that mediates the interaction between the target protein and E3 ubiquitin ligase and passes through ubiquitin - The proteasome system achieves specific degradation
of the target protein.
With a different mechanism of action from traditional small molecule inhibitors, PROTAC has attracted much attention
from industry and academia in recent years due to its potential to target proteins that were previously considered undruggable and overcome drug resistance.
However, due to the molecular properties of PROTAC, it is still difficult to design highly selective, highly active, oral PROTAC molecules
.
Therefore, there is an urgent need to build a comprehensive PROTAC information system to help researchers rationally design
PROTAC.

In October 2022, Professor Hou Tingjun's research group at the School of Pharmacy of Zhejiang University published the paper "PROTAC-DB 2.
0: an updated" in the important international biomedical journal Nucleic Acids Research database of PROTACs", a major update
to the original PROTAC-DB.
Founded in 2020, PROTAC-DB is the first PROTAC online data platform, which includes a variety of data including chemical structure, biological activity, physicochemical properties, etc.
, and has now become PROTAC An important data resource for
the field.
At the beginning of its publication, the platform was recommended by Professor Crews, founder of PROTAC, and has been repeatedly reviewed by Nature Reviews Drug Discovery and Chemical Society Reviews and other international authoritative journals have been positively cited and introduced, and the number of visits to the platform has exceeded 75,000 times, which is a highly cited paper
by ESI.

PROTAC 2.
0 has three major updates
.
First, PROTAC 2.
0 significantly increases the number of PROTAC molecules included and the corresponding variety of data (from 1662 PROTAC molecules to 3270 in the original generation).
pcs).

Secondly, considering that only a small amount of PROTAC-mediated ternary complex crystal structure has been solved experimentally, its structural information can provide great help
for the rational design of PROTAC.
Therefore, in version 2.
0, the authors used the self-developed PROTAC-Model modeling method to construct the corresponding ternary complex calculation model for the active PROTAC molecules, which assisted the researchers in structure-based construction PROTAC rational design
.
Finally, PROTAC 2.
0 further optimizes the interactive interface to bring a more user-friendly experience
.
All data is accessible
through the http://cadd.
zju.
edu.
cn/protacdb/.

   The School of Pharmacy of Zhejiang University is the first signatory of this paper, doctoral student Weng Gaoqi is the first author, and Professor Hou Tingjun and Associate Professor Li Dan of the School of Pharmacy of Zhejiang University are the co-corresponding authors
.

Original link: https://academic.
oup.
com/nar/advance-article/doi/10.
1093/nar/gkac946/6775390