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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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 +7 more sources
The Dual Interactions of p53 with MDM2 and p300: Implications for the Design of MDM2 Inhibitors. [PDF]
Int J Mol Sci, 2019 Proteins that limit the activity of the tumour suppressor protein p53 are increasingly being targeted for inhibition in a variety of cancers. In addition to the development of small molecules, there has been interest in developing constrained (stapled) peptide inhibitors. A stapled peptide ALRN_6924 that activates p53 by preventing its interaction with
Kannan S +3 more
europepmc +7 more sources
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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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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Fortifying p53 - beyond Mdm2 inhibitors. [PDF]
Aging (Albany NY), 2016 The tumor suppressor p53 is mutated in roughly 50% of all human malignancies. However, in the other 50% of tumors which retain wildtype p53, it appears insufficiently active to confer tumor suppression, through cell cycle arrest or apoptosis. Much of this p53-inactivation occurs through the Mdm2 oncoprotein, the product of a p53-inducible gene. Mdm2 is
Sriraman A, Li Y, Dobbelstein M.
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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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Photoactivation of MDM2 Inhibitors: Controlling Protein-Protein Interaction with Light. [PDF]
J Am Chem Soc, 2018 Selectivity remains a major challenge in anticancer therapy, which potentially can be overcome by local activation of a cytotoxic drug. Such triggered activation can be obtained through modification of a drug with a photoremovable protecting group (PPG), and subsequent irradiation in the chosen place and time.
Hansen MJ +5 more
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