ArticleACS chemical biology2020
Selective Degradation of GSPT1 by Cereblon Modulators Identified via a Focused Combinatorial Library.
Article in ACS chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 83 citations in OpenAlex.
- High-throughput ligand diversification to discover chemical inducers of proximity.Nature chemical biology · 2026Article
- TNG961 Is a Selective Oral HBS1L Molecular Glue Degrader for the Treatment of FOCAD-Deleted Cancers.Cancer discovery · 2026Article
- The synthetic landscape of cereblon (CRBN) binders: from thalidomide to emerging chemotypes.Chemical Society reviews · 2026Review
- Degron-independent recruitment of KAT2A expands the target space of CRBN molecular glues.Science (New York, N.Y.) · 2026Article
- Molecular glue degraders: Rational design, specificity engineering, and advanced delivery.Acta pharmaceutica Sinica. B · 2026Review
- Advances in molecular glue degraders for targeted protein degradation: Focus on NEK7, WEE1, CDK2, GSPT1 and VAV1.Asian journal of pharmaceutical sciences · 2026Review
- Article
- Exploring Novel E3 Ligases and Neosubstrates for Molecular Glue Degraders and Therapeutic Applications in Cancer.Oncology research · 2026Review
- Property-Based Optimization of Cereblon-Based Molecular Glue Degraders.ACS medicinal chemistry letters · 2025Review
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- Quantifying Cooperativity through Binding Free Energies in Molecular Glue Degraders.Journal of chemical theory and computation · 2025Article
- Development of Potent and Selective CK1α Molecular Glue Degraders.Journal of medicinal chemistry · 2025Article
- Discovery of CRBN-Dependent WEE1 Molecular Glue Degraders from a Multicomponent Combinatorial Library.Journal of the American Chemical Society · 2024Article
- Molecular glues for protein-protein interactions: Progressing toward a new dream.Cell chemical biology · 2024Review
- Applications of protein ubiquitylation and deubiquitylation in drug discovery.The Journal of biological chemistry · 2024Review
- SuFEx-based chemical diversification for the systematic discovery of CRBN molecular glues.Bioorganic & medicinal chemistry · 2024Article
- Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Targeted protein degradation in CNS disorders: a promising route to novel therapeutics?Frontiers in molecular neuroscience · 2024Review
- Design principles for cyclin K molecular glue degraders.Nature chemical biology · 2024Article
- A platform for the rapid synthesis of molecular glues (Rapid-Glue) under miniaturized conditions for direct biological screening.European journal of medicinal chemistry · 2023Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Cereblon (CRBN) is an E3 ligase adapter protein that can be reprogrammed by imide-class compounds such as thalidomide, lenalidomide, and pomalidomide to induce the degradation of neo-substrate proteins. In order to identify additional small molecule CRBN modulators, we implemented a focused combinatorial library approach where we fused an imide-based CRBN-binding pharmacophore to a heterocyclic scaffold, which could be further elaborated. We screened the library for CRBN-dependent antiproliferative activity in the multiple myeloma cell line MM1.S and identified five hit compounds. Quantitative chemical proteomics of hit compounds revealed that they induced selective degradation of GSPT1, a translation termination factor that is currently being explored as a therapeutic target for the treatment of acute myeloid leukemia. Molecular docking studies with CRBN and GSPT1 followed by analogue synthesis identified a possible hydrogen bond interaction with the central pyrimidine ring as a molecular determinant of hit compounds' selectivity. This study demonstrates that a focused combinatorial library design, phenotypic screening, and chemical proteomics can provide a suitable workflow to efficiently identify novel CRBN modulators.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.