AI Article Synopsis

  • Researchers developed in-vitro assay methods to assess how compounds interact with the peroxisome proliferator-activated receptor gamma (PPARγ), an important target for various metabolic disorders.
  • They created specific plasmids for testing both the gene expression triggered by PPARγ and the binding activity of various compounds using a competitive binding assay technique called time-resolved fluorescence resonance energy transfer (TR-FRET).
  • Among tested compounds, ZLJ01 was identified as having strong binding affinity to PPARγ without triggering gene activation, and it showed promise in enhancing insulin-stimulated glucose uptake in liver cells in preliminary tests.

Article Abstract

In-vitro assay methods were established to evaluate transactivation and binding activity of compounds on peroxisome proliferator-activated receptor y (PPARγ). Firstly, plasmids were constructed for transactivation assay of PPARγ response element (PPRE) triggered reporter gene expression, and for cell-based binding activity assay of the chimeric receptor, which was fused with PPARγ ligand binding domain (LBD) and yeast transcriptional activator Gal4. Secondly, by using PPARy competitive binding assay based on time resolved-fluorescence resonance energy transfer (TR-FRET), affinities of compounds and drugs to PPARγ were evaluated. In application of these above methods, the PPARγ activating potency and characteristics of different compounds were evaluated, and a novel benzeneselfonamide derivative, ZLJ01, was found to have comparable binding activity and affinity with the well-known PPARy agonist, but lack of PPRE mediated transactivation activity. In preliminary study on in-vitro hypoglycemic activity, ZLJ1 was found to promote insulin-stimulated glucose uptake by liver cells. Therefore, we believe that combining transactivation and binding activity as well as affinity evaluation, the system could be used to screen non-agonist PPARγ ligand as anovel PPARγ modulator

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