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Related Concept Videos

Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
The Proteasome Structure01:17

The Proteasome Structure

The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.

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Updated: Jun 23, 2026

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

Published on: November 9, 2020

On-Demand Activatable PROTACs for Targeted Protein Degradation.

Caiyun Guo1, Zhibin Ren1, Xiaomei Wu1

  • 1State Key Laboratory of Chemical Resource Engineering, MOE Key Lab of Biomedical Materials of Natural Macromolecules, Beijing University of Chemical Technology, Beijing, China.

Chemistry (Weinheim an Der Bergstrasse, Germany)
|June 20, 2026
PubMed
Summary
This summary is machine-generated.

Activatable Proteolysis-targeting chimeras (PROTACs) offer precise control over protein degradation, overcoming limitations of conventional therapies. This review explores three key types of activatable PROTACs for enhanced therapeutic applications.

Keywords:
PROTACsactivationcancerprodrugtargeted protein degradation

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The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)
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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
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The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)
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The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)

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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

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

Published on: May 15, 2019

Area of Science:

  • Biomedical Research
  • Molecular Biology
  • Drug Discovery

Background:

  • Targeted protein degradation (TPD) is a revolutionary approach in biomedicine.
  • Proteolysis-targeting chimeras (PROTACs) are bifunctional molecules with significant therapeutic potential, especially in oncology and autoimmune diseases.
  • PROTACs leverage the ubiquitin-proteasome system (UPS) to degrade target proteins, offering advantages over traditional inhibitors for 'undruggable' targets.

Purpose of the Study:

  • To review the design principles and progress of activatable PROTACs.
  • To address the translational challenges of conventional PROTACs, such as poor tissue specificity and toxicity.
  • To highlight the development of on-demand activatable PROTAC prodrugs for spatiotemporally precise protein degradation.

Main Methods:

  • Systematic review of scientific literature on activatable PROTACs.
  • Categorization of activatable PROTACs into three main types: endogenously, photo-activatable, and bioorthogonally activatable.
  • Comparative analysis of the advantages and limitations of each category.

Main Results:

  • Activatable PROTACs enable precise control over protein degradation, overcoming limitations of conventional PROTACs.
  • Three major categories of activatable PROTACs have emerged: endogenously, exogenously photo-activatable, and bioorthogonally activatable.
  • Each strategy presents unique merits and limitations influencing their therapeutic applicability.

Conclusions:

  • Activatable PROTACs represent a significant advancement in targeted protein degradation.
  • Understanding the different activation strategies is crucial for optimizing therapeutic outcomes.
  • Further research and development in activatable PROTACs are essential for clinical translation and advancing novel therapeutics.