Abstract
The discovery of the key negative regulator MDM2 (mouse double minute 2, also termed HDM2 for its human equivalent) provided a great opportunity to manipulate the levels of the tumor suppressor p53 in cancer cells. Activation of p53 in tumor cells by inhibiting the interaction of MDM2 with p53 has therefore been the focus of a large effort in drug discovery. The modulation of protein-protein interactions, however, has historically been very difficult to achieve owing to the large surface area of interaction. In this article, we review the recent accomplishments in this area and our quest for a clinically viable MDM2 inhibitor.
Keywords: mdm2, p53, small molecule inhibitor, peptidic inhibitor, protein-protein interaction
Current Topics in Medicinal Chemistry
Title: Small Molecule Inhibitors of p53/MDM2 Interaction
Volume: 5 Issue: 2
Author(s): Nader Fotouhi and Bradford Graves
Affiliation:
Keywords: mdm2, p53, small molecule inhibitor, peptidic inhibitor, protein-protein interaction
Abstract: The discovery of the key negative regulator MDM2 (mouse double minute 2, also termed HDM2 for its human equivalent) provided a great opportunity to manipulate the levels of the tumor suppressor p53 in cancer cells. Activation of p53 in tumor cells by inhibiting the interaction of MDM2 with p53 has therefore been the focus of a large effort in drug discovery. The modulation of protein-protein interactions, however, has historically been very difficult to achieve owing to the large surface area of interaction. In this article, we review the recent accomplishments in this area and our quest for a clinically viable MDM2 inhibitor.
Export Options
About this article
Cite this article as:
Fotouhi Nader and Graves Bradford, Small Molecule Inhibitors of p53/MDM2 Interaction, Current Topics in Medicinal Chemistry 2005; 5 (2) . https://dx.doi.org/10.2174/1568026053507705
DOI https://dx.doi.org/10.2174/1568026053507705 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Genetics of the First Seven Proprotein Convertase Enzymes in Health and Disease
Current Genomics Imatinib (STI571) Resistance in Chronic Myelogenous Leukemia: Molecular Basis of the Underlying Mechanisms and Potential Strategies for Treatment
Mini-Reviews in Medicinal Chemistry Role of Alterations in the Apoptotic Machinery in Sensitivity of Cancer Cells to Treatment
Current Pharmaceutical Design Radiopharmaceuticals in Tumor Hypoxia Imaging: A Review Focused on Medicinal Chemistry Aspects
Anti-Cancer Agents in Medicinal Chemistry Targeting Angiogenesis in Soft Tissue Sarcomas
Current Angiogenesis (Discontinued) Bcl-2 Targeted-Therapy for the Treatment of Head and Neck Squamous Cell Carcinoma
Recent Patents on Anti-Cancer Drug Discovery Management of Vulvar Cancer
Reviews on Recent Clinical Trials Lymphatic Targeting of Nanosystems for Anticancer Drug Therapy
Current Pharmaceutical Design Tyrosine Kinases as Molecular Targets to Inhibit Cancer Progression and Metastasis
Current Pharmaceutical Design Molecular Mechanism Behind the Synergistic Activity of Diphenylmethyl Selenocyanate and Cisplatin Against Murine Tumor Model
Anti-Cancer Agents in Medicinal Chemistry T-Cell Zeta Chain Expression, Phosphorylation and Degradation and their Role in T-Cell Signal Transduction and Immune Response Regulation in Health And Disease
Current Signal Transduction Therapy Giant Cell Arteritis – A Series of Cases and Review of Literature
Current Rheumatology Reviews Targeting Calmodulin in Reversing Multi Drug Resistance in Cancer Cells
Mini-Reviews in Medicinal Chemistry Beneficial and Adverse Effects of Molecularly Targeted Therapies for Acute Promyelocytic Leukemia in Central Nervous System
CNS & Neurological Disorders - Drug Targets Small Molecule Inhibitors of Stat3 Signaling Pathway
Current Cancer Drug Targets Fungal Proteins with Antiproliferative and Anticancer Activities
Protein & Peptide Letters Evaluation of Vitamin C as a Personalized Adjuvant Medicine: Pharmacogenomic Studies
Current Pharmacogenomics and Personalized Medicine Role of Dendritic Cells in HIV-Immunotherapy
Current HIV Research Secretory Clusterin as a Novel Molecular-targeted Therapy for Inhibiting Hepatocellular Carcinoma Growth
Current Medicinal Chemistry A Focus on Heme Oxygenase-1 (HO-1) Inhibitors
Current Medicinal Chemistry