PPARγ ligands and their therapeutic applications: a patent review (2008 - 2014)

Abstract

Introduction: PPARγ regulates glucose and lipid metabolism, immunity, and cellular growth and differentiation. Thiazolidinediones (TZDs) are synthetic PPARγ ligands that are used in the treatment of type 2 diabetes. However, TZDs can cause adverse effects, such as increased risks of heart failure, bone fractures and bladder cancer. PPARγ has a large ligand-binding pocket, which makes it possible to develop a variety of PPARγ ligands, leading to patents on their therapeutic applications.

Areas covered: We summarize recent patent activity regarding PPARγ ligands and their therapeutic applications from 2008. Pharmacologic methods to increase PPARγ expression and to decrease PPARγ adverse effects by combining PPARγ ligands with other drugs are also reviewed.

Expert opinion: In addition to novel PPARγ ligands that exhibit selective therapeutic activity without adverse effects, such as bone loss, fluid retention or weight gain, methods for the combination of PPARγ ligands and other compounds have been claimed to decrease adverse effects and/or to enhance targeted effects. Combination therapy is useful but has the potential risk of unexpected adverse effects. Patent applications for expanding clinical application of PPARγ ligands to non-metabolic diseases, such as neurological and inflammatory diseases, and to skin whitening have been filed, and future studies are needed to elucidate the underlying mechanisms.

Keywords: adverse effects; bone; combinations; diabetes; inflammation; neurological diseases; nuclear receptors; selective modulators; skin.