ArticleOncology research2025
Discovery and Characterization of Novel IKZF1/3 Glue Degraders against Multiple Hematological Cancer Cell Lines.
Article in Oncology research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- CD47-mediated efferocytosis in diseases: A comprehensive review.Molecular biology reports · 2026Review
- Bridging E3 Ligase Binding and Targeted Degradation Through Fluorescence Polarization.International journal of molecular sciences · 2026Article
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objectives: Immunomodulatory drugs (IMiDs), functioning as molecular glue degraders, have been approved for treating various hematological malignancies; however, the inevitable acquired drug resistance resulting from their skeletal similarity and hematological toxicities poses significant obstacles to their clinical treatment. The study aimed to develop degraders with potent efficiency and low toxicity. Methods: Phenotypic profiling, elaborate structure-activity relationships (SAR), rational drug design and degradation profiles investigations, quantitative proteomics analysis and cell-based functional studies, and pharmacokinetic studies were conducted to develop more potent degraders. Results: This study developed novel CRBN-binding moieties through methylene deletion in lenalidomide's isoindole core. Lead compounds MGD-A7 and MGD-C9 demonstrated superior antiproliferative efficacy vs. IMiDs, with submicromolar potency. MGD-A7 and MGD-C9 significantly and selectively induced the degradation of Ikaros Family Zinc Finger Proteins 1 and 3 (IKZF1/3) with nanomolar potency via a CRBN-dependent pathway. Mechanistically, MGD-A7 and MGD-C9 dramatically induced cell apoptosis and G1 cell cycle arrest and MGD-C9 exhibited favorable pharmacokinetic properties Conclusions: These results indicate that MGD-C9 could act as a highly effective CRBN ligand and is expected to become a candidate drug for the treatment of hematological malignancies.
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