Small-Molecule Inhibitors of the MDM2–p53 Protein–Protein Interaction (MDM2 Inhibitors) in Clinical Trials for Cancer Treatment

WAF1, a potential mediator of p53 tumor suppression

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A Single Nucleotide Polymorphism in the MDM2 Promoter Attenuates the p53 Tumor Suppressor Pathway and Accelerates Tumor Formation in Humans

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Drugging the p53 pathway: understanding the route to clinical efficacy

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Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy

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Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition

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Structure-based design of potent non-peptide MDM2 inhibitors

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MDMX: a novel p53‐binding protein with some functional properties of MDM2.

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Discovery of RG7388, a Potent and Selective p53–MDM2 Inhibitor in Clinical Development

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Functions of the MDM2 oncoprotein

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Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study

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MDM2 inhibitors for cancer therapy

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Reduction of p53 gene dosage does not increase initiation or promotion but enhances malignant progression of chemically induced skin tumors

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Discovery and Cocrystal Structure of Benzodiazepinedione HDM2 Antagonists That Activate p53 in Cells

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Discovery of RG7112: a small-molecule MDM2 inhibitor in clinical development

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Squamous Cell Carcinoma of the Lung: Molecular Subtypes and Therapeutic Opportunities

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SAR405838: An Optimized Inhibitor of MDM2–p53 Interaction That Induces Complete and Durable Tumor Regression

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MDM2 is a Central Node in the p53 Pathway: 12 Years and Counting

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The p53 family in differentiation and tumorigenesis

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A Potent Small-Molecule Inhibitor of the MDM2–p53 Interaction (MI-888) Achieved Complete and Durable Tumor Regression in Mice

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Discovery of AMG 232, a Potent, Selective, and Orally Bioavailable MDM2–p53 Inhibitor in Clinical Development

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Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms

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p53-based Cancer TherapyPreprint

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Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery

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Mdm2: The Ups and Downs

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Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction

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Structure-Based Design of Novel Inhibitors of the MDM2–p53 Interaction

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The Structure‐Based Design of Mdm2/Mdmx–p53 Inhibitors Gets Serious

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Isoindolinone Inhibitors of the Murine Double Minute 2 (MDM2)-p53 Protein−Protein Interaction: Structure−Activity Studies Leading to Improved Potency

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Small-Molecule Inhibitors of the MDM2-p53 Protein−Protein Interaction Based on an Isoindolinone Scaffold

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Discovery and Optimization of Chromenotriazolopyrimidines as Potent Inhibitors of the Mouse Double Minute 2−Tumor Protein 53 Protein−Protein Interaction

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Mutational spectrum of p53 mutations in primary breast and ovarian tumors

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Robust Generation of Lead Compounds for Protein–Protein Interactions by Computational and MCR Chemistry: p53/Hdm2 Antagonists

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Acquisition of p53 mutations in response to the non-genotoxic p53 activator Nutlin-3

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Discovery, Synthesis, and Biological Evaluation of Orally Active Pyrrolidone Derivatives as Novel Inhibitors of p53–MDM2 Protein–Protein Interaction

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Overexpression of MDM2, due to enhanced translation, results in inactivation of wild-type p53 in Burkitt's lymphoma cells

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Isoindolinone-based inhibitors of the MDM2–p53 protein–protein interaction

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Activation of p53 by the MDM2 inhibitor RG7112 impairs thrombopoiesis

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Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for Potential Clinical Development

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Small-molecule inhibitors of MDM2 as new anticancer therapeutics

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Synthesis, in Vitro, and in Cell Studies of a New Series of [Indoline-3,2′-thiazolidine]-Based p53 Modulators

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Selective and Potent Morpholinone Inhibitors of the MDM2–p53 Protein–Protein Interaction

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Identification of the Spiro(oxindole-3,3′-thiazolidine)-Based Derivatives as Potential p53 Activity Modulators

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Regulation of MDMX Expression by Mitogenic Signaling

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Detection of MDM2 gene amplification or protein expression distinguishes sclerosing mesenteritis and retroperitoneal fibrosis from inflammatory well-differentiated liposarcoma

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MDM2 induces hyperplasia and premalignant lesions when expressed in the basal layer of the epidermis

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Inhibitors of the p53/hdm2 protein–protein interaction—path to the clinic

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The central valine concept provides an entry in a new class of non peptide inhibitors of the p53–MDM2 interaction

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Targeting the MDM2-p53 protein–protein interaction for new cancer therapeutics

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Ordering of the N-Terminus of Human MDM2 by Small Molecule Inhibitors

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The p53-MDM2/MDMX axis – A chemotype perspective

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Phase 1 dose escalation, food effect, and biomarker study of RG7388, a more potent second-generation MDM2 antagonist, in patients (pts) with solid tumors.

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Small-Molecule Inhibitors of p53-MDM2 Interaction: the 2006-2010 Update

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Novel Inhibitors of the MDM2-p53 Interaction Featuring Hydrogen Bond Acceptors as Carboxylic Acid Isosteres

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Structure-based design, synthesis, and biological evaluation of novel 1,4-diazepines as HDM2 antagonists

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Exhaustive Fluorine Scanning toward Potent p53–Mdm2 Antagonists

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An Expeditious Synthesis of the MDM2–p53 Inhibitor AM-8553

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Improvement of the synthesis and pharmacokinetic properties of chromenotriazolopyrimidine MDM2-p53 protein-protein inhibitors

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Synthesis and evaluation of novel orally active p53–MDM2 interaction inhibitors

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Enantiomerically pure 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists

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Inhibitors of MDM2 and MDMX: A Structural Perspective

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Pivotal Role of an Aliphatic Side Chain in the Development of an HDM2 Inhibitor

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Identification of novel inhibitors of p53–MDM2 interaction facilitated by pharmacophore-based virtual screening combining molecular docking strategy

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Substituted piperidines as HDM2 inhibitors

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Core modification of substituted piperidines as Novel inhibitors of HDM2–p53 protein–protein interaction

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Small molecules, big targets: drug discovery faces the protein–protein interaction challenge

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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

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Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia

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Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials

Zhu, H., Gao, H., Ji, Y., Zhou, Q., Du, Z., Tian, L., Jiang, Y., Yao, K., & Zhou, Z. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01314-3 · Cited by 223 · see citing works

Discovery of 4-((3′ <i>R</i> ,4′ <i>S</i> ,5′ <i>R</i> )-6″-Chloro-4′-(3-chloro-2-fluorophenyl)-1′-ethyl-2″-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3″-indoline]-5′-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development

Aguilar, A., Lu, J., Liu, L., Du, D., Bernard, D., McEachern, D., Przybranowski, S., Li, X., Luo, R., Wen, B., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01665 · Cited by 211 · see citing works

State-of-the-art strategies for targeting protein–protein interactions by small-molecule inhibitors

Sheng, C., Dong, G., Miao, Z., Zhang, W., & Wang, W. (2015) · Chemical Society Reviews · doi:10.1039/c5cs00252d · Cited by 165 · see citing works

Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy: advances and perspectives

Fang, Y., Liao, G., & Yu, B. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.01.003 · Cited by 106 · see citing works

Homo-PROTAC mediated suicide of MDM2 to treat non-small cell lung cancer

He, S., Ma, J., Fang, Y., Liu, Y., Wu, S., Dong, G., Wang, W., & Sheng, C. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.11.022 · Cited by 91 · see citing works

Dose and Schedule Determine Distinct Molecular Mechanisms Underlying the Efficacy of the p53–MDM2 Inhibitor HDM201

Jeay, S., Ferretti, S., Holzer, P., Fuchs, J., Chapeau, E. A., Wartmann, M., Sterker, D., Romanet, V., Murakami, M., Kerr, G., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0338 · Cited by 87 · see citing works

Discovery of a novel class of highly potent inhibitors of the p53–MDM2 interaction by structure-based design starting from a conformational argument

Furet, P., Masuya, K., Kallen, J., Stachyra-Valat, T., Ruetz, S., Guagnano, V., Holzer, P., Mah, R., Stutz, S., Vaupel, A., et al. (2016) · Bioorganic &amp; Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.08.010 · Cited by 80 · see citing works

Development of selective small molecule MDM2 degraders based on nutlin

Wang, B., Wu, S., Liu, J., Yang, K., Xie, H., & Tang, W. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.05.046 · Cited by 77 · see citing works

Rational drug design, synthesis, and biological evaluation of novel chiral tetrahydronaphthalene-fused spirooxindole as MDM2-CDK4 dual inhibitor against glioblastoma

Wang, B., Peng, F., Huang, W., Zhou, J., Zhang, N., Sheng, J., Haruehanroengra, P., He, G., & Han, B. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.12.013 · Cited by 73 · see citing works

Potent effect of the MDM2 inhibitor AMG232 on suppression of glioblastoma stem cells

Her, N.-G., Oh, J.-W., Oh, Y. J., Han, S., Cho, H. J., Lee, Y., Ryu, G. H., & Nam, D.-H. (2018) · Cell Death &amp; Disease · doi:10.1038/s41419-018-0825-1 · Cited by 68 · see citing works

Small molecules targeting protein–protein interactions for cancer therapy

Wu, D., Li, Y., Zheng, L., Xiao, H., Ouyang, L., Wang, G., & Sun, Q. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.05.035 · Cited by 71 · see citing works

Resistance mechanisms to TP53-MDM2 inhibition identified by in vivo piggyBac transposon mutagenesis screen in an Arf ^−/− mouse model

Chapeau, E. A., Gembarska, A., Durand, E. Y., Mandon, E., Estadieu, C., Romanet, V., Wiesmann, M., Tiedt, R., Lehar, J., de Weck, A., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620262114 · Cited by 64 · see citing works

Role of p53 circuitry in tumorigenesis: A brief review

Niazi, S., Purohit, M., & Niazi, J. H. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.08.099 · Cited by 65 · see citing works

The development of piperidinones as potent MDM2-P53 protein-protein interaction inhibitors for cancer therapy

Liao, G., Yang, D., Ma, L., Li, W., Hu, L., Zeng, L., Wu, P., Duan, L., & Liu, Z. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.09.044 · Cited by 63 · see citing works

A phase I trial of the human double minute 2 inhibitor (MK-8242) in patients with refractory/recurrent acute myelogenous leukemia (AML)

Ravandi, F., Gojo, I., Patnaik, M. M., Minden, M. D., Kantarjian, H., Johnson-Levonas, A. O., Fancourt, C., Lam, R., Jones, M. B., Knox, C. D., et al. (2016) · Leukemia Research · doi:10.1016/j.leukres.2016.07.004 · Cited by 57 · see citing works

Helping the released guardian: Drug combinations for supporting the anticancer activity of HDM2 (MDM2) antagonists

Kocik, J., Machula, M., Wisniewska, A., Surmiak, E., Holak, T. A., & Skalniak, L. (2019) · Cancers · doi:10.3390/cancers11071014 · Cited by 46 · see citing works

Small-molecule inhibition of MDM2-p53 interaction augments radiation response in human tumors

Werner, L. R., Huang, S., Francis, D. M., Armstrong, E. A., Ma, F., Li, C., Iyer, G., Canon, J., & Harari, P. M. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-1056-t · Cited by 45 · see citing works

CDK4 inhibition diminishes p53 activation by MDM2 antagonists

Sriraman, A., Dickmanns, A., Najafova, Z., Johnsen, S. A., & Dobbelstein, M. (2018) · Cell Death &amp; Disease · doi:10.1038/s41419-018-0968-0 · Cited by 40 · see citing works

Therapeutic inhibition of the MDM2-p53 interaction prevents recurrence of adenoid cystic carcinomas

Nör, F., Warner, K. A., Zhang, Z., Acasigua, G. A., Pearson, A. T., Kerk, S. A., Helman, J. I., Sant'Ana Filho, M., Wang, S., & Nör, J. E. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1235 · Cited by 37 · see citing works

Initial Testing (Stage 1) of MK‐8242—A Novel MDM2 Inhibitor—by the Pediatric Preclinical Testing Program

Kang, M. H., Reynolds, C. P., Kolb, E. A., Gorlick, R., Carol, H., Lock, R., Keir, S. T., Maris, J. M., Wu, J., Lyalin, D., et al. (2016) · Pediatric Blood &amp; Cancer · doi:10.1002/pbc.26064 · Cited by 36 · see citing works

Inhibition of P53-murine double minute 2 (MDM2) interactions with 3,3′-spirocyclopentene oxindole derivatives

Gicquel, M., Gomez, C., Garcia Alvarez, M. C., Pamlard, O., Guérineau, V., Jacquet, E., Bignon, J., Voituriez, A., & Marinetti, A. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01137 · Cited by 34 · see citing works

MDM2 inhibition in the treatment of glioblastoma: From concept to clinical investigation

Pellot Ortiz, K. I., Rechberger, J. S., Nonnenbroich, L. F., Daniels, D. J., & Sarkaria, J. N. (2023) · Biomedicines · doi:10.3390/biomedicines11071879 · Cited by 30 · see citing works

DETERMINING QUALITY REQUIREMENTS AT THE UNIVERSITIES TO IMPROVE THE QUALITY OF EDUCATION

Mustafa, N. H., Kelesbayev, D., & Alibekova, Z. D. (2018) · The Journal of Economic Research & Business Administration · doi:10.26577/be-2018-2-2141

The regulation of MDM2 oncogene and its impact on human cancers

YuHan, Zhao, Haiyang, Yu, Wenwei, & Hu (2014) · 生物化学与生物物理学报：英文版 · Cited by 1 · see citing works

Anticancer strategies by upregulating p53 through inhibition of its ubiquitination by MDM2

Anifowose, A., Agbowuro, A. A., Yang, X., & Wang, B. (2020) · Medicinal Chemistry Research · doi:10.1007/s00044-020-02574-9 · Cited by 25 · see citing works

Oncogenic c-Myc-induced lymphomagenesis is inhibited non-redundantly by the p19Arf–Mdm2–p53 and RP–Mdm2–p53 pathways

Meng, X., Zhang, Y., Dong, J., et al. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/7k14-b379 · Cited by 1 · see citing works

Mechanism-specific signatures for small-molecule p53 activators

van Leeuwen, I. M. M., Higgins, M., Campbell, J., Brown, C. J., McCarthy, A. R., Pirrie, L., Westwood, N. J., & Laı́n, S. (2011) · Cell Cycle · doi:10.4161/cc.10.10.15519 · Cited by 52 · see citing works