Reprofiling of Troglitazone Towards More Active and Less Toxic Derivatives: A New Hope for Cancer Treatment?
| Autor: | Marine Geoffroy, Andrea Bordessa, Michel Boisbrun, Sandra Kuntz, Stéphane Flament, Sabine Mazerbourg, Isabelle Grillier-Vuissoz, Audrey Berthe |
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| Přispěvatelé: | Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug hepatotoxicity medicine.drug_class media_common.quotation_subject Peroxisome proliferator-activated receptor Antineoplastic Agents [SDV.CAN]Life Sciences [q-bio]/Cancer thiazolidinedione Drug reprofiling Pharmacology troglitazone Structure-Activity Relationship 03 medical and health sciences In vivo Drug Discovery medicine Animals Humans cancer Chromans Thiazolidinedione media_common chemistry.chemical_classification diabetes business.industry Drug Repositioning Troglitazone Cancer General Medicine medicine.disease 3. Good health PPAR gamma Drug repositioning 030104 developmental biology Diabetes Mellitus Type 2 Liver chemistry Cancer cell Hepatocytes Thiazolidinediones business medicine.drug |
| Zdroj: | Current Topics in Medicinal Chemistry Current Topics in Medicinal Chemistry, Bentham Science Publishers, 2016, 16 (19), pp.2115-2124. ⟨10.2174/1568026616666160216153036⟩ |
| ISSN: | 1568-0266 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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