T0070907(IC50=1 nM) , an effective and specific PPARγ inhibitor, with the >800-fold selectivity over PPARα and PPARδ.

PPARα:0.85 μM (Ki), PPARγ:1 nM, PPARδ:1.8 μM (Ki)

T0070907 can attenuate the beneficial effects of lipopolysaccharide pretreatment, such as significantly improving renal insufficiency, reducing hepatocyte damage and circulatory failure, and reducing plasma interleukin-1 elevation caused by severe endotoxemia.

Ligand Binding Assay: To determine the binding affinity of T0070907 to the PPARs, scintillation proximity assay (SPA) is performed with the following modifications. A 90-μl reaction contains SPA buffer (10 mm KH2PO4, 10 mm KH2PO4, 2 mm EDTA, 50 mm NaCl, 1 mm dithiothreitol, 2 mmCHAPS, 10% (v/v) glycerol, pH 7.1), 50 ng of GST-PPARγ (or 150 ng of GST-PPARα, GST-PPARδ), 5 nm 3H-labeled radioligands, and 5 μl of T0070907 in Me2SO. After incubation for 1 h at room temperature, 10 μl of polylysine-coated SPA beads (at 20 mg/ml in SPA buffer) are added, and the mixtureis incubated for 1 h before reading in Packard Topcount. [3H]Rosiglitazone is used for PPARγ, and [3H]GW2433 is used for PPARα and PPARδ.

MTS assay(Only for Reference)