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Related Experiment Video

Updated: Jul 26, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

Recent Advances in Pro-PROTAC Development to Address On-Target Off-Tumor Toxicity.

Chuanjie Chen^1,2, Yiwen Yang³, Zhe Wang³

¹Drug Discovery & Development Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Journal of Medicinal Chemistry

|June 15, 2023

Summary

Proteolysis-targeting chimeras (PROTACs) offer targeted protein degradation but face on-target, off-tumor toxicity. Prodrug-based PROTACs (pro-PROTACs) are emerging to enhance tumor-specific delivery and minimize side effects.

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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Area of Science:

Biochemistry
Molecular Biology
Drug Discovery

Background:

Proteolysis-targeting chimera (PROTAC) technology enables targeted protein degradation.
PROTACs show promise for treating various diseases, including cancer.
On-target, off-tumor toxicity in healthy cells is a significant challenge for PROTAC clinical applications.

Purpose of the Study:

To highlight innovative strategies for enhancing cell-selective PROTAC activity.
To discuss prodrug-based PROTACs (pro-PROTACs) for tumor-targeted release.
To explore the potential of pro-PROTACs in expanding PROTAC technology applications.

Main Methods:

Review of current research on PROTAC technology.
Analysis of strategies for achieving cell-selective protein degradation.
Exploration of prodrug approaches for targeted PROTAC delivery.

Main Results:

Prodrug-based PROTACs (pro-PROTACs) offer a strategy for tumor-targeted release.
These approaches aim to minimize on-target, off-tumor toxicity.
Pro-PROTACs may broaden the therapeutic applications of PROTAC technology.

Conclusions:

Innovative prodrug strategies are crucial for safe and effective PROTAC-based cancer therapy.
Pro-PROTACs represent a promising advancement in targeted protein degradation.
Further development of pro-PROTACs could significantly impact drug development and clinical outcomes.