Abstract
The existence of unresponsive tumors and the appearance of resistant tumors during the course of treatments both justify that we increase urgently the panel of pharmacological molecules able to fight cancer. An interesting strategy is drug reprofiling (also known as drug repositioning, drug repurposing or drug retasking) that consists of identifying and developing new uses for existing drugs. This review illustrates drug reprofiling with troglitazone (TGZ), a synthetic PPARγ agonist initially used for the treatment of type II diabetes. The fact that TGZ also displays anticancer effects is known since the end of the nineties but its development as an anticancer agent was slowed down due to hepatotoxic side effects. Part of the knowledge available for TGZ, mainly the molecular basis for PPARγ activation, its metabolization pathways and the side effects on hepatocytes, were taken into account to elaborate new molecules. Key findings were that unsaturated TGZ derivatives, when compared to TGZ, do not activate PPARγ, exhibit a higher efficiency on cancer cells and a lower toxicity towards hepatocytes. However, a weakness is that the mechanisms involved in the anticancer effects are still not completely understood and that the efficiency of such derivatives has not yet been completely studied in vivo. Data about this point should become available very soon from animal models and this will be a prerequisite to initiate clinical trials with these potential new anticancer drugs developed from a drug repurposing strategy.
Keywords: Drug reprofiling, Troglitazone, Thiazolidinedione, Cancer, Diabetes, Hepatotoxicity.
Current Topics in Medicinal Chemistry
Title:Reprofiling of Troglitazone Towards More Active and Less Toxic Derivatives: A New Hope for Cancer Treatment?
Volume: 16 Issue: 19
Author(s): Sabine Mazerbourg, Sandra Kuntz, Isabelle Grillier-Vuissoz, Audrey Berthe, Marine Geoffroy, Stéphane Flament, Andrea Bordessa and Michel Boisbrun
Affiliation:
Keywords: Drug reprofiling, Troglitazone, Thiazolidinedione, Cancer, Diabetes, Hepatotoxicity.
Abstract: The existence of unresponsive tumors and the appearance of resistant tumors during the course of treatments both justify that we increase urgently the panel of pharmacological molecules able to fight cancer. An interesting strategy is drug reprofiling (also known as drug repositioning, drug repurposing or drug retasking) that consists of identifying and developing new uses for existing drugs. This review illustrates drug reprofiling with troglitazone (TGZ), a synthetic PPARγ agonist initially used for the treatment of type II diabetes. The fact that TGZ also displays anticancer effects is known since the end of the nineties but its development as an anticancer agent was slowed down due to hepatotoxic side effects. Part of the knowledge available for TGZ, mainly the molecular basis for PPARγ activation, its metabolization pathways and the side effects on hepatocytes, were taken into account to elaborate new molecules. Key findings were that unsaturated TGZ derivatives, when compared to TGZ, do not activate PPARγ, exhibit a higher efficiency on cancer cells and a lower toxicity towards hepatocytes. However, a weakness is that the mechanisms involved in the anticancer effects are still not completely understood and that the efficiency of such derivatives has not yet been completely studied in vivo. Data about this point should become available very soon from animal models and this will be a prerequisite to initiate clinical trials with these potential new anticancer drugs developed from a drug repurposing strategy.
Export Options
About this article
Cite this article as:
Mazerbourg Sabine, Kuntz Sandra, Grillier-Vuissoz Isabelle, Berthe Audrey, Geoffroy Marine, Flament Stéphane, Bordessa Andrea and Boisbrun Michel, Reprofiling of Troglitazone Towards More Active and Less Toxic Derivatives: A New Hope for Cancer Treatment?, Current Topics in Medicinal Chemistry 2016; 16 (19) . https://dx.doi.org/10.2174/1568026616666160216153036
DOI https://dx.doi.org/10.2174/1568026616666160216153036 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
- Announcements
Related Articles
-
TGF-Beta Type I Receptor (Alk5) Kinase Inhibitors in Oncology
Current Pharmaceutical Biotechnology RNA Interference-Mediated Validation of Survivin and Apollon/BRUCE as New Therapeutic Targets for Cancer Therapy
Current Topics in Medicinal Chemistry Folate Based Radiopharmaceuticals for Imaging and Therapy of Cancer and Inflammation
Current Pharmaceutical Design Peptides Targeting Angiogenesis Related Growth Factor Receptors
Current Pharmaceutical Design A hypothesis for the role of RECK in angiogenesis
Current Vascular Pharmacology Predicting LncRNA-Disease Association Based on Generative Adversarial Network
Current Gene Therapy Cerebrovascular Complications of Diabetes: SGLT-2 Inhibitors as a Promising Future Therapeutics
Current Drug Targets AFM-Based Single Molecule Techniques: Unraveling the Amyloid Pathogenic Species
Current Pharmaceutical Design Cytochrome P450 Drug Metabolizing Enzymes in Roma Population Samples: Systematic Review of the Literature
Current Medicinal Chemistry Follow the ATP: Tumor Energy Production: A Perspective
Anti-Cancer Agents in Medicinal Chemistry Clinical Significance of miR-1826 as a Novel Prognostic Biomarker in Colorectal Cancer
Anti-Cancer Agents in Medicinal Chemistry Metabolite Identification in NMR-based Metabolomics
Current Metabolomics MicroRNAs as Diagnostic, Prognostic and Predictive Biomarkers of Ovarian Cancer
Recent Patents on Biomarkers Androgen Pathway Related Gene Variants and Prostate Cancer Association in Auckland Men
Current Pharmacogenomics and Personalized Medicine Therapy of Hepatocellular Carcinoma with Rhenium-188 Lipiodol
Current Radiopharmaceuticals MicroRNA in the Pathogenesis and Prognosis of Esophageal Cancer
Current Pharmaceutical Design DNA Damage-inducing Compounds: Unraveling their Pleiotropic Effects Using High Throughput Sequencing
Current Medicinal Chemistry 99mTc-labeling of Peptidomimetic Antagonist to Selectively Target αvβ3 Receptor-Positive Tumor: Comparison of PDA and EDDA as Co-Ligands
Current Radiopharmaceuticals Licochalcone B Arrests Cell Cycle Progression and Induces Apoptosis in Human Breast Cancer MCF-7 Cells
Recent Patents on Anti-Cancer Drug Discovery Targeting Translation for Treatment of Cancer - A Novel Role for IRES?
Current Cancer Drug Targets