The Development of INT131 as a Selective PPAR𝜸 Modulator: Approach to a Safer Insulin Sensitizer

Figure 3

Selective PPARγ modulation separates dose response curves of different PPARγ effects. Left: PPARγ full agonists activate the range of receptor responses in a linked fashion. Hence, increasing concentration (or dose) increases responses in concert. In the clinical setting, higher doses of TZDs produce greater efficacy as well as greater side effects. Right: selective PPAR modulation is response and context-dependent. Depending on the cellular setting and the response being measured, SPPARM activity may have different potency (top) or different maximal activity (efficacy, bottom) compared to a full agonist. Hence, increasing concentration (or dose) may lead to increases in some responses without linked increases in others. This offers the potential in the clinical setting for separation of antidiabetic efficacy from side effects such as edema and weight gain.