MDM2 inhibitors for cancer therapy

p53 Mutations in Human Cancers

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Surfing the p53 network

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In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2

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Mdm2 promotes the rapid degradation of p53

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Regulation of p53 stability by Mdm2

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Live or let die: the cell's response to p53

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The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation

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Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain

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The p53 pathway: positive and negative feedback loops

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Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53

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Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53

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Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53

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Post‐translational modifications and activation of p53 by genotoxic stresses

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Decision making by p53: life, death and cancer

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The MDM2 gene amplification database

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p53 and Human Cancer: The First Ten Thousand Mutations

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Inactivation of the apoptosis effector Apaf-1 in malignant melanoma

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Inhibiting the p53–MDM2 interaction: an important target for cancer therapy

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The p53–Mdm2 module and the ubiquitin system

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Small molecule RITA binds to p53, blocks p53–HDM-2 interaction and activates p53 function in tumors

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Pirh2, a p53-Induced Ubiquitin-Protein Ligase, Promotes p53 Degradation

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

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Structure-Based Design of Spiro-oxindoles as Potent, Specific Small-Molecule Inhibitors of the MDM2−p53 Interaction

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The ubiquitin ligase COP1 is a critical negative regulator of p53

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Structure-based design of potent non-peptide MDM2 inhibitors

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Functions of the MDM2 oncoprotein

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The role of p53 in determining sensitivity to radiotherapy

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Rescuing the function of mutant p53

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ARF-BP1/Mule Is a Critical Mediator of the ARF Tumor Suppressor

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Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53

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Transcription-independent pro-apoptotic functions of p53

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

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MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy

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Design of a synthetic Mdm2-binding mini protein that activates the p53 response in vivo

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Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4

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Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells

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Mdm4 (Mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development

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

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Amplification of <i>Mdmx</i> (or <i>Mdm4</i> ) Directly Contributes to Tumor Formation by Inhibiting p53 Tumor Suppressor Activity

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Small-Molecule Antagonists of p53-MDM2 Binding: Research Tools and Potential Therapeutics

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Mdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells <i>in vivo</i>

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P53 and Prognosis

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MDM2 Is a Negative Regulator of p21 , Independent of p53

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<i>mdm2</i> Is Critical for Inhibition of p53 during Lymphopoiesis and the Response to Ionizing Irradiation

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MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells

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Phosphorylation of p53 on Key Serines Is Dispensable for Transcriptional Activation and Apoptosis

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Rapid p53 sequence analysis in primary lung cancer using an oligonucleotide probe array

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Dial 9-1-1 for p53: Mechanisms of p53 Activation by Cellular Stress

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Retinoids: present role and future potential

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Tumor suppression and normal aging in mice with constitutively high p53 activity

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Targeting the p53–MDM2 interaction to treat cancer

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Activation of p53 by MDM2 Antagonists Can Protect Proliferating Cells from Mitotic Inhibitors

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Levels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3

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Comparative study of the p53-mdm2 and p53-MDMX interfaces

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An shRNA barcode screen provides insight into cancer cell vulnerability to MDM2 inhibitors

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Mdmx as an essential regulator of p53 activity

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Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma

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P53 and PrognosisNew Insights and Further Complexity

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p53 Activation by Small Molecules: Application in Oncology

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Benzodiazepinedione inhibitors of the Hdm2:p53 complex suppress human tumor cell proliferation in vitro and sensitize tumors to doxorubicin in vivo

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Synergistic activation of p53 by inhibition of MDM2 expression and DNA damage

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Exploiting cancer cell cycling for selective protection of normal cells.

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Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL)

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Targeting protein–protein interactions for cancer therapy

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Synergistic roles of Mdm2 and Mdm4 for p53 inhibition in central nervous system development

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Targeting E3 Ubiquitin Ligases for Cancer Therapy

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Prospective therapeutic applications of p53 inhibitors

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A small synthetic peptide, which inhibits the p53-hdm2 interaction, stimulates the p53 pathway in tumour cell lines 1 1Edited by A. R. Fersht

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Quantitative analysis of estrogen receptor-? mRNA and its variants in human breast cancers

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Discovery of a Nanomolar Inhibitor of the Human Murine Double Minute 2 (MDM2)−p53 Interaction through an Integrated, Virtual Database Screening Strategy

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Death squads enlisted by the tumour suppressor p53

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Pretreatment with DNA-damaging agents permits selective killing of checkpoint-deficient cells by microtubule-active drugs

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Aberrant regulation and function of wild-type p53 in radioresistant melanoma cells.

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NMR indicates that the small molecule RITA does not block p53-MDM2 binding in vitro

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Unleashing the power of p53: lessons from mice and men: Figure 1.Preprint

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Enhanced pharmacokinetic properties of 1,4-benzodiazepine-2,5-dione antagonists of the HDM2-p53 protein–protein interaction through structure-based drug design

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Structure and Organization of Amplified DNA on Double Minutes Containing the mdm2 Oncogene

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Novel 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists with improved cellular activity

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Novel Antisense Anti-MDM2 Mixed-Backbone Oligonucleotides: Proof of Principle, In Vitro and In Vivo Activities, and Mechanisms

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No longer a molecular black box – new clues to apoptosis and drug resistance in melanoma

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p53 as a therapeutic target: unresolved issues on the road to cancer therapy targeting mutant p53

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Small Molecule Inhibitors of p53/MDM2 Interaction

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Selective protection of normal proliferating cells against the toxic effects of chemotherapeutic agents.

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The first 30 years of p53: growing ever more complex.

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Principles of cancer therapy: oncogene and non-oncogene addiction

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Awakening guardian angels: drugging the p53 pathway

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Acetylation Is Indispensable for p53 Activation

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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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Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction to Reactivate p53 Function: A Novel Approach for Cancer Therapy

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Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy

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Hdm2 is a ubiquitin ligase of Ku70-Akt promotes cell survival by inhibiting Hdm2-dependent Ku70 destabilization

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PAHSAs reduce cellular senescence and protect pancreatic beta cells from metabolic stress through regulation of Mdm2/p53

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Nutlin-3 Affects Expression and Function of Retinoblastoma Protein

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

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

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Restoration of p53 using the novel MDM2-p53 antagonist APG115 suppresses dedifferentiated papillary thyroid cancer cells

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Peptide Activators of the p53 Tumor Suppressor

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mdm2: a bridge over the two tumour suppressors, p53 and Rb

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