SR1664

SR1664 is a potent, selective non-thiazolidinedione small molecule that acts as a peroxisome proliferator–activated receptor gamma (PPARγ) antagonist and modulator. Unlike classical PPARγ agonists (such as thiazolidinediones), SR1664 binds tightly to the PPARγ receptor but does not exhibit transcriptional agonism. Instead, it blocks cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of PPARγ at Ser273—a mechanism linked to insulin sensitization—without causing side effects typical of full agonists like weight gain or fluid retention. In preclinical models, SR1664 improves glucose homeostasis and insulin sensitivity without affecting bone mineralization or inducing other adverse effects associated with traditional PPARγ-targeting drugs[1][2][3][9]. It has been studied primarily for its anti-diabetic activity.

Other names

PPARγ Modulator, SR1664(S)-4′-((2,3-dimethyl-5-(1-(4-nitrophenyl)ethylcarbamoyl)-1H-indol-1-yl)methyl)biphenyl-2-carboxylic acid