ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Development of MDM2-Targeting PROTAC for Advancing Bone Regeneration.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed.
- From undruggable to degradable: A deep learning-enabled framework for precision orthopaedic protein degradation.Journal of orthopaedic translation · 2026Review
- PROTAC-Mediated Targeted Degradation of MDM2 Induces Tumor-Suppressive Signaling in Osteosarcoma Cells.Cells · 2026Article
- PROTAC-Mediated Degradation of mHTT Aggregates Attenuates Neurotoxicity in Cellular and R6/2 Mouse Models of Huntington's Disease.Journal of the American Chemical Society · 2026Article
- HSP70 Interactome-Mediated Proteolysis Targeting Chimera (HSP70-PROTAC) for Ferroptosis-Driven Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- E3 ubiquitin ligases in bone homeostasis: from regulatory mechanisms to skeletal diseases and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Rational design of the linkers in targeting chimeras.Chemical science · 2025Review
- 3D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in rats.Bioactive materials · 2025Article
- Development of MDM2-Targeting PROTAC for Advancing Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Proteolysis-targeting chimeras (PROTACs) degrade target proteins through the ubiquitin-proteasome system. To date, PROTACs are primarily used to treat various diseases; however, they have not been applied in regenerative therapy. Herein, this work introduces MDM2-targeting PROTACs customized for application in bone regeneration. An MDM2-PROTAC library is constructed by combining Nutlin-3 and CRBN ligands with various linker designs. Through a multistep validation process, this work develops MDM2-PROTACs (CL144 and CL174) that presented potent degradation efficiency and a robust inductive effect on the biomineralization. Next, this work performs whole-transcriptome analysis to dissect the biological effects of the CL144, and reveals the upregulation of osteogenic marker genes. Furthermore, CL144 effectively induced bone regeneration in bone graft and ovariectomy (OVX) models after local and systemic administration, respectively. In the OVX model, the combination treatment with CL144 and alendronate induced a synergistic effect. Overall, this study demonstrates the promising role of MDM2-PROTAC in promoting bone regeneration, marking the first step toward expanding the application of the PROTAC technology.
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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.