Abstract
MDM2 protein negatively regulates p53 and is found to be elevated in cancer cells. An attractive approach towards targeting MDM2 is the use of small molecule inhibitors that bind to MDM2 and disrupt the MDM2-p53 interaction. Our laboratory has been at the forefront in testing MDM2 inhibitors in pancreatic adenocarcinoma (PaCa), a deadly disease with ~50% wild-type p53 population. Emerging evidence suggests that apart from regulating p53, MDM2 can influence other key molecules involved in cancer. This review summarizes recent advancements in the development of MDM2 inhibitors, their novel primary and secondary targets and highlights their potential as therapeutics for PaCa.
Keywords: MDM2 and p53, small molecule inhibitors, pancreatic cancer
Mini-Reviews in Medicinal Chemistry
Title: MDM2 Inhibitors for Pancreatic Cancer Therapy
Volume: 10 Issue: 6
Author(s): A.S. Azmi, P.A. Philip, K. Almhanna, F.W. Beck, Z.K. Kafri, F.H. Sarkar and R.M. Mohammad
Affiliation:
Keywords: MDM2 and p53, small molecule inhibitors, pancreatic cancer
Abstract: MDM2 protein negatively regulates p53 and is found to be elevated in cancer cells. An attractive approach towards targeting MDM2 is the use of small molecule inhibitors that bind to MDM2 and disrupt the MDM2-p53 interaction. Our laboratory has been at the forefront in testing MDM2 inhibitors in pancreatic adenocarcinoma (PaCa), a deadly disease with ~50% wild-type p53 population. Emerging evidence suggests that apart from regulating p53, MDM2 can influence other key molecules involved in cancer. This review summarizes recent advancements in the development of MDM2 inhibitors, their novel primary and secondary targets and highlights their potential as therapeutics for PaCa.
Export Options
About this article
Cite this article as:
Azmi A.S., Philip P.A., Almhanna K., Beck F.W., Kafri Z.K., Sarkar F.H. and Mohammad R.M., MDM2 Inhibitors for Pancreatic Cancer Therapy, Mini-Reviews in Medicinal Chemistry 2010; 10 (6) . https://dx.doi.org/10.2174/138955710791384054
DOI https://dx.doi.org/10.2174/138955710791384054 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
- 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
Related Articles
-
Cholinergic Targets in Lung Cancer
Current Pharmaceutical Design Cancer/Testis Antigens Trigger Epithelial-Mesenchymal Transition and Genesis of Cancer Stem-Like Cells
Current Pharmaceutical Design Role of NF-κB in the Regulation of Cytochrome P450 Enzymes
Current Drug Metabolism Weekly Low-doses with Prolonged Infusion of Gemcitabine /Cisplatin for Multi-treated Metastatic Breast Cancer Patients
Current Cancer Therapy Reviews Nitrogen Mustards as Anticancer Chemotherapies: Historic Perspective, Current Developments and Future Trends
Current Topics in Medicinal Chemistry Carbonic Anhydrase Inhibitors and the Management of Cancer
Current Topics in Medicinal Chemistry Resisting the Resistance in Cancer: Cheminformatics Studies on Short- Path Base Excision Repair Pathway Antagonists Using Supervised Learning Approaches
Combinatorial Chemistry & High Throughput Screening Cranberry for Urinary Tract Infection: From Bench to Bedside
Current Topics in Medicinal Chemistry Novel Methods for the Non-Invasive Administration of DNA Therapeutics and Vaccines
Current Drug Delivery Fluorinated Natural Products with Clinical Significance
Current Topics in Medicinal Chemistry Synthesis and Anti-cancer Activities of Apigenin Derivatives
Medicinal Chemistry Role of Neuromodulation and Optogenetic Manipulation in Pain Treatment
Current Neuropharmacology Progress and Prospects: The Use of 3D Spheroid Model as a Relevant Way to Study and Optimize DNA Electrotransfer
Current Gene Therapy Iron Chelators for the Treatment of Cancer
Current Medicinal Chemistry Use of Thiazolidinediones and Risk of Bladder Cancer: Disease or Drugs?
Current Drug Safety A Review on Anti-Cancer Activity of Some of the Oil-Soluble Organosulphur Compounds Against Colon Cancer
Current Traditional Medicine Alzheimer’s Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy
Current Pharmaceutical Design GH-Inhibitory Activity of Novel Somatostatin Agonists: Potential Applications in Acromegaly
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Induction of GST and Related Events by Dietary Phytochemicals: Sources, Chemistry, and Possible Contribution to Chemoprevention
Current Topics in Medicinal Chemistry Current and Future Development of Estrogen Receptor Ligands: Applications in Estrogen-Related Cancers
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery