Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials [PDF]
Journal of Hematology & Oncology, 2022 p53, encoded by the tumor suppressor gene TP53, is one of the most important tumor suppressor factors in vivo and can be negatively regulated by MDM2 through p53–MDM2 negative feedback loop.
Haohao Zhu +8 more
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MDM2 inhibitors: Targeting p53-MDM2 interaction to anti-cancer [PDF]
E3S Web of Conferences, 2021 P53 is a recognized tumor suppressor gene, which mainly depends on the activity of its transfer factor to realize the tumor suppressor effect. Mouse two-minute 2 (MDM2) is an important inhibitor of p53.
Zhang Xulin
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MDM2 inhibitors in cancer immunotherapy: Current status and perspective [PDF]
Genes and DiseasesMurine double minute 2 (MDM2) plays an essential role in the cell cycle, apoptosis, DNA repair, and oncogene activation through p53-dependent and p53-independent signaling pathways.
Qinru Zeng +8 more
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Strategies for p53 Activation and Targeted Inhibitors of the p53-Mdm2/MdmX Interaction
Cellsp53 is a tumor suppressor gene and is regarded as one of the most crucial genes in protecting humans against cancer. The protein Mdm2 and its homolog MdmX serve as negative regulators of p53.
Ye Huang +6 more
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Recent Small-Molecule Inhibitors of the p53–MDM2 Protein–Protein Interaction
Molecules, 2020 This review presents the last decade of studies on the synthesis of various types of small-molecule inhibitors of the p53– Mouse double minute 2 homolog (MDM2) protein–protein interaction.
Anastasia Beloglazkina +3 more
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Artificial Macrocycles as Potent p53-MDM2 Inhibitors. [PDF]
ACS Med Chem Lett, 2017 Based on a combination of an Ugi four component reaction and a ring closing metathesis, a library of novel artificial macrocyclic inhibitors of the p53-MDM2 interaction was designed and synthesized. These macrocycles, alternatively to stapled peptides, target for the first time the large hydrophobic surface area formed by Tyr67, Gln72, His73, Val93 ...
Estrada-Ortiz N +5 more
europepmc +6 more sources
Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy: advances and perspectives
Acta Pharmaceutica Sinica B, 2020 Blocking the MDM2/X–P53 protein–protein interaction has been widely recognized as an attractive therapeutic strategy for the treatment of cancers. Numerous small-molecule MDM2 inhibitors have been reported since the release of the structure of the MDM2 ...
Yuan Fang, Guochao Liao, Bin Yu
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MDM2 inhibitors, nutlin-3a and navtemadelin, retain efficacy in human and mouse cancer cells cultured in hypoxia [PDF]
Scientific Reports, 2023 Activation of p53 by small molecule MDM2 inhibitors can induce cell cycle arrest or death in p53 wildtype cancer cells. However, cancer cells exposed to hypoxia can develop resistance to other small molecules, such as chemotherapies, that activate p53 ...
Ada Lerma Clavero +9 more
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Resistance acquisition to MDM2 inhibitors
Biochemical Society Transactions, 2014 Various experimental strategies aim to (re)activate p53 signalling in cancer cells. The most advanced clinically are small-molecule inhibitors of the autoregulatory interaction between p53 and MDM2 (murine double minute 2). Different MDM2 inhibitors are currently under investigation in clinical trials.
Jindrich, Cinatl +3 more
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Strategic selection of MDM2 inhibitors enhances the efficacy of FAK inhibition in mesothelioma based on TP53 genotype. [PDF]
PLoS ONEMesothelioma has characteristic genetic changes including inactivation of neurofibromatosis type 2 (NF2) and deletion of the INK4A/ARF region. Cells deficient of NF2 protein (MERLIN) depend on focal adhesion kinase (FAK) for cell adhesion and FAK ...
Xuerao Ning +7 more
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