Related Experiment Video
Updated: Oct 23, 2025
10:44
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
13.4K
Developments of CRBN-based PROTACs as potential therapeutic agents
Chao Wang1, Yujing Zhang2, Yudong Wu1
1The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, Shandong, China.
European Journal of Medicinal Chemistry
|August 19, 2021
Summary
Protease-targeted chimeras (PROTACs) harness the ubiquitin system for targeted protein degradation. This review focuses on Cereblon (CRBN)-based PROTACs, highlighting their broad therapeutic potential beyond cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Protease-targeted chimeras (PROTACs) represent an innovative therapeutic modality.
- PROTACs function by recruiting E3 ubiquitin ligases to induce targeted protein degradation.
- Heterobifunctional PROTACs comprise an E3 ligase ligand, a linker, and a target protein ligand.
Purpose of the Study:
- To provide a comprehensive update on recent advancements in Cereblon (CRBN)-based PROTACs.
- To review the therapeutic applications of CRBN-based PROTACs across various disease areas.
- To discuss the future prospects and challenges associated with CRBN-based PROTAC technology.
Main Methods:
- Literature review of CRBN-based PROTAC research.
- Categorization of PROTACs by disease area and target class.
- Systematic presentation of degradants, alphabetized by target.
Main Results:
- Identification of various small-molecule PROTACs, including CRBN, VHL, IAPs, MDM2, DCAF15, DCAF16, and RNF114-based systems.
- CRBN-based PROTACs (e.g., ARV-110, ARV-471) show significant therapeutic promise.
- CRBN-based PROTACs have demonstrated efficacy in cancer, cardiovascular, immune, neurodegenerative, and infectious diseases.
Conclusions:
- CRBN-based PROTACs are a rapidly advancing field with broad therapeutic applicability.
- Continued research is crucial for overcoming potential challenges and realizing the full potential of PROTACs.
- CRBN-based PROTACs offer a promising new avenue for disease treatment.
Related Concept Videos
01:26Targets for Drug Action: Overview
8.2K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
8.2K
01:27Transducer Mechanism: Enzyme-Linked Receptors
3.2K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
3.2K
01:28Preclinical Development: Overview
5.3K
Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
5.3K
01:28Structure-Activity Relationships and Drug Design
1.2K
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
1.2K
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
802
Angina pectoris, a primary symptom of ischemic heart disease, requires careful pharmacological interventions. In this context, calcium channel blockers (CCBs) and ranolazine have emerged as crucial pharmacotherapeutic agents, providing deep insights into the complexities of angina management.
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
802
01:16Therapeutic Drug Monitoring: Overview and Classification
49
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood at designated intervals to ensure the drug concentration stays within a therapeutic range. This monitoring is crucial for optimizing individual dosage regimens, enhancing therapeutic efficacy, and minimizing drug-related toxicity. TDM is vital for drugs with narrow therapeutic windows, significant variability in pharmacokinetics, and a clear correlation between plasma levels and...
49