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Updated: May 15, 2026

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
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Discovery of INT131: a selective PPARγ modulator that enhances insulin sensitivity
Joshua P Taygerly1, Lawrence R McGee, Steven M Rubenstein
1Amgen, Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. josh.taygerly@gmail.com
Abstract:
PPARγ is a member of the nuclear hormone receptor family and plays a key role in the regulation of glucose homeostasis. This Letter describes the discovery of a novel chemical class of diarylsulfonamide partial agonists that act as selective PPARγ modulators (SPPARγMs) and display a unique pharmacological profile compared to the thiazolidinedione (TZD) class of PPARγ full agonists. Herein we report the initial discovery of partial agonist 4 and the structure-activity relationship studies that led to the selection of clinical compound INT131 (3), a potent PPARγ partial agonist that displays robust glucose-lowering activity in rodent models of diabetes while exhibiting a reduced side-effects profile compared to marketed TZDs.
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