ArticleScientific reports2016
The use of the NEDD8 inhibitor MLN4924 (Pevonedistat) in a cyclotherapy approach to protect wild-type p53 cells from MLN4924 induced toxicity.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- An Anti-Invasive Role for Mdmx through the RhoA GTPase under the Control of the NEDD8 Pathway.Cells · 2024Article
- CDK4/6 inhibition confers protection of normal gut epithelia against gemcitabine and the active metabolite of irinotecan.Cell cycle (Georgetown, Tex.) · 2023Article
- Selective protection of normal cells from chemotherapy, while killing drug-resistant cancer cells.Oncotarget · 2023Review
- Article
- The Anti-Tumor Activity of the NEDD8 Inhibitor Pevonedistat in Neuroblastoma.International journal of molecular sciences · 2021Article
- Inhibiting Neddylation with MLN4924 Suppresses Growth and Delays Multicellular Development inBiomolecules · 2021Article
- Structure Based Design of Bicyclic Peptide Inhibitors of RbAp48.Angewandte Chemie (International ed. in English) · 2021Article
- The transcription co-factor JAB1/COPS5, serves as a potential oncogenic hub of human chondrosarcoma cellsAmerican journal of cancer research · 2021Article
- Article
- The Identification of Potential Therapeutic Targets for Cutaneous Squamous Cell Carcinoma.The Journal of investigative dermatology · 2020Article
- Breaking the Fourth Wall: Modulating Quaternary Associations for Protein Regulation and Drug Discovery.Chembiochem : a European journal of chemical biology · 2019Review
- Small molecule activators of the p53 response.Journal of molecular cell biology · 2019Review
- Chk1 inhibitor SCH 900776 enhances the antitumor activity of MLN4924 on pancreatic cancer.Cell cycle (Georgetown, Tex.) · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targetting the ubiquitin pathway is an attractive strategy for cancer therapy. The inhibitor of the ubiquitin-like molecule NEDD8 pathway, MLN4924 (Pevonedistat) is in Phase II clinical trials. Protection of healthy cells from the induced toxicity of the treatment while preserving anticancer efficacy is a highly anticipated outcome in chemotherapy. Cyclotherapy was proposed as a promising approach to achieve this goal. We found that cytostatic activation of p53 protects cells against MLN4924-induced toxicity and importantly the effects are reversible. In contrast, cells with mutant or no p53 remain sensitive to NEDD8 inhibition. Using zebrafish embryos, we show that MLN4924-induced apoptosis is reduced upon pre-treatment with actinomycin D in vivo. Our studies show that the cellular effects of NEDD8 inhibition can be manipulated based on the p53 status and that NEDD8 inhibitors can be used in a p53-based cyclotherapy protocol to specifically target cancer cells devoid of wild type p53 function, while healthy cells will be protected from the induced toxicity.
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