L-764406 Is a Partial Agonist of Human Peroxisome Proliferator-activated Receptor γ

α,β-Unsaturated Ketone Is a Core Moiety of Natural Ligands for Covalent Binding to Peroxisome Proliferator-activated Receptor γ

“…Although 9(S)-HODE and 13(S)-HODE have structures quite similar to those of 9-oxoODE and 13-oxoODE, respectively, they lack an ␣,␤-unsaturated ketone and did not covalently bind to the PPAR␥ LBD, indicating that the ␣,␤-unsaturated ketone was a crucial structure for the covalent binding. It is reported that synthetic ligands GW9662, T0070907, and L-764406 covalently bind to the cysteine residue in the PPAR␥ LBD (21)(22)(23). In this assay, we were able to confirm the cysteine modification by T0070907 (Fig.…”

“…Meanwhile, it has been reported that a natural PPAR␥ ligand, 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), has the potential to bind covalently to some proteins, such as H-Ras (16), NF-B (17,18), IB kinase (19), and AP-1 (20) via a cysteine residue. In addition, it is reported that the synthetic PPAR␥ ligands GW9662, T0070907, and L-764406 (21)(22)(23) have been shown to react with the cysteine residue of the PPAR␥ LBD. These lines of evidence led to us investigate the binding mode of 15d-PGJ 2 to the PPAR␥ LBD.…”

Analogues of the Epoxy Resin Monomer Diglycidyl Ether of Bisphenol F: Effects on Contact Allergenic Potency and Cytotoxicity

“…32,35 It is unknown at present if DGEBA covalently modifies the PPARγ receptor. 47 It is anticipated that DGEBF causes cell death by similar mechanisms to DGEBA due to their structural similarity. The relative loss in cytotoxic potency of the two linear epoxides 5 and 6 compared to DGEBF may indicate that terminal epoxides are not the only structural feature required for potent cytotoxicity in this cell line.…”

Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: Evidence for an antiinflammatory role for lipoprotein lipase

“…The 3 H 2 -labeled known synthetic PPAR agonists used were compound A and compound B (see Supporting Methods) with relative K d s as follows: compound A, PPAR␥ 2.5 nM and PPAR␣ 5.0 nM; compound B, PPAR␦ 1.0 nM (27,28). Results are expressed as the percentage inhibition with a calculated inhibitory constant (K iS ).…”

“…Scintillation proximity assays were done using human full-length cDNA for PPAR␣, PPAR␦, and hPPAR␥ 2 subcloned into the pGEX-KT expression vector as described (27). The 3 H 2 -labeled known synthetic PPAR agonists used were compound A and compound B (see Supporting Methods) with relative K d s as follows: compound A, PPAR␥ 2.5 nM and PPAR␣ 5.0 nM; compound B, PPAR␦ 1.0 nM (27,28).…”