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Mini Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01093

The Pioglitazone trek via human PPAR gamma: From discovery to a medicine at the FDA and beyond

 PALLAVI R. DEVCHAND1, 2*, Tianyun liu3,  Russ B. Altman3, 4, Garret A. Fitzgerald5 and  Eric E. Schadt2
  • 1Department of Physiology and Pharmacology, University of Calgary, Canada
  • 2Genomics and Genetics, Icahn School of Medicine at Mount Sinai, United States
  • 3Departments of Genetics, School of Medicine, Stanford University, United States
  • 4Department of Bioengineering, Stanford University, United States
  • 5Perelman School of Medicine, University of Pennsylvania, United States

For almost two decades, pioglitazone has been prescribed primarily to prevent and treat insulin resistance in some type 2 diabetic patients. In this review, we trace the path to discovery of pioglitazone as a thiazolidinedione compound, the glitazone tracks through the regulatory agencies, the trek to molecular agonism in the nucleus and the binding of pioglitazone to the nuclear receptor PPARgamma. Given the rise in consumption of pioglitazone in T2D patients worldwide and the increased number of clinical trials currently testing alternate medical uses for this drug, there is also merit to some reflection on the reported adverse effects.Going forward, it is imperative to continue investigations into the mechanisms of actions of pioglitazone, the potential of glitazone drugs to contribute to unmet needs in complex diseases associated with the dynamics of adaptive homeostasis, and also the routes to minimizing adverse effects in every-day patients throughout the world.

Keywords: pioglitazone, PPAR gamma, Protein-drug interactions, nuclear hormone receptor, glitazone medications

Received: 20 Jun 2018; Accepted: 07 Sep 2018.

Edited by:

Annalisa Bruno, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy

Reviewed by:

Annalisa Trenti, Università degli Studi di Padova, Italy
Lina Ghibelli, Università degli Studi di Roma Tor Vergata, Italy  

Copyright: © 2018 DEVCHAND, liu, Altman, Fitzgerald and Schadt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. PALLAVI R. DEVCHAND, University of Calgary, Department of Physiology and Pharmacology, Calgary, T2N 1N4, Alberta, Canada, Pallavidevchand@aol.com