Related Experiment Video
Updated: Oct 15, 2025
10:44
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
13.4K
Ligands for cereblon: 2017-2021 patent overview
Alexander Kazantsev1, Mikhail Krasavin1
1Institute of Chemistry, Saint Petersburg State University, Saint Petersburg, Russian Federation.
Expert Opinion on Therapeutic Patents
|October 27, 2021
Summary
New research reviews Cereblon (CRBN) ligands, crucial for targeted protein degradation via PROTACs. The study highlights the comprehensive patenting of thalidomide-like CRBN ligands and the emerging potential of novel, non-thalidomide-like chemotypes.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Drug Discovery
Background:
- Cereblon (CRBN) is a key substrate receptor for the CRL4CRBN E3 ubiquitin ligase.
- CRBN is the target for immunomodulatory drugs (IMiDs) and a crucial component in proteolysis-targeting chimeras (PROTACs).
- PROTACs facilitate targeted protein degradation using the cell's ubiquitin-proteasome system.
Purpose of the Study:
- To review the patent landscape and design strategies for CRBN ligands.
- To explore both 'thalidomide-like' and novel non-thalidomide-like CRBN-binding compounds.
- To emphasize the role of rational, crystallography-driven approaches in discovering new CRBN ligands.
Main Methods:
- Literature review focusing on patent activity and scientific publications related to CRBN ligands.
- Categorization of CRBN ligands into 'thalidomide-like' and 'non-thalidomide-like' structures.
- Analysis of rational design and structure-based approaches for CRBN ligand development.
Main Results:
- Patent literature extensively covers CRBN ligands related to classical IMiDs (thalidomide, lenalidomide, pomalidomide).
- Significant research interest exists in identifying novel, non-thalidomide-like chemotypes that bind to CRBN.
- Structure-based design and academic research are advancing the discovery of new CRBN ligands.
Conclusions:
- The chemical space of IMiD-related CRBN ligands is well-documented in patents.
- Developing non-thalidomide-like CRBN ligands represents a promising frontier in drug discovery.
- Crystallography-driven and rational design methods are pivotal for future CRBN ligand innovation.
Related Concept Videos
02:40Ligand Binding Sites
14.2K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
14.2K
00:49Ligand Binding and Linkage
5.1K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.1K
01:19Ligand-gated Ion Channels
13.1K
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
13.1K
01:26Drug Discovery: Overview
9.5K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
9.5K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.0K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
3.0K
01:28Preclinical Development: Overview
5.2K
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...
5.2K