ArticleJournal of medicinal chemistry2019
Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis Targeting Chimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable Tumor Regression.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 295 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- The synthetic landscape of cereblon (CRBN) binders: from thalidomide to emerging chemotypes.Chemical Society reviews · 2026Review
- RING finger E3 ubiquitin ligases: novel therapeutic opportunities in melanoma.Cellular & molecular biology letters · 2026Review
- The application of drug delivery systems based on targeted protein degradation chimeras in disease treatment strategies.Journal of nanobiotechnology · 2026Review
- Epithelial-to-mesenchymal transition as a central driver of tumor cell plasticity.Nature cancer · 2026Review
- Insights into the Design of MYC-Targeting Proteolysis Targeting Chimeras (PROTACs).Molecules (Basel, Switzerland) · 2026Article
- Prospects and advances of PROTAC in the treatment of hematologic malignancies.Experimental hematology & oncology · 2026Review
- PROTAC-Mediated Targeted Degradation of MDM2 Induces Tumor-Suppressive Signaling in Osteosarcoma Cells.Cells · 2026Article
- E3 ubiquitin ligases: structural diversity, dysregulation in disease, and their emerging role in targeted therapeutic strategies.Frontiers in molecular biosciences · 2026Review
- Multi-scale classification decodes the complexity of the human E3 ligome.Nature communications · 2025Article
- PROTAC repurposing uncovers a noncanonical binding surface that mediates chemical degradation of nuclear receptors.Nature communications · 2025Article
- Discovery of dCDK9-202 as a Highly Potent and Selective PROTAC CDK9 Degrader with StrongJournal of medicinal chemistry · 2025Article
- Characterization of a dual degrader of MDM2 and GSPT1.European journal of medicinal chemistry · 2025Article
- The Ubiquitin-Proteasome System in Asthma: Mechanisms and Therapeutic Possibilities.Clinical reviews in allergy & immunology · 2025Review
- C(spJournal of the American Chemical Society · 2025Article
- Dual functionality of MDM2 in PROTACs expands the horizons of targeted protein degradation.Biomarker research · 2025Review
- Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs.Communications chemistry · 2025Review
- MD-4251: A First-in-Class Oral MDM2 Degrader Inducing Complete Tumor Regression with Single-Dose Administration.Journal of medicinal chemistry · 2025Article
- Structure-Based Design of PROTACS for the Degradation of Soluble Epoxide Hydrolase.Journal of medicinal chemistry · 2025Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Human murine double minute 2 (MDM2) protein is a primary endogenous cellular inhibitor of the tumor suppressor p53 and has been pursued as an attractive cancer therapeutic target. Several potent, nonpeptide, small-molecule inhibitors of MDM2 are currently in clinical development. In this paper, we report our design, synthesis, and evaluation of small-molecule MDM2 degraders based on the proteolysis targeting chimera (PROTAC) concept. The most promising compound (MD-224) effectively induces rapid degradation of MDM2 at concentrations <1 nM in human leukemia cells. It achieves an IC
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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.