AOPs Including This Stressor
|Antagonist binding to PPARα leading to body-weight loss||High|
Events Including This Stressor
|Binding as antagonist, Antagonist binding to PPARalpha ligand binding domain|
|Binding of antagonist, PPAR alpha|
|stabilization, PPAR alpha co-repressor|
GW6471 - Specifically designed molecules such as the PPARα antagonists GW6471 can bind to PPARα selectively recruiting binding of co-repressors to the PPARα nuclear signaling complex (Xu et al 2002).
In Xu et al (2002), X-ray crystallography was used to characterize the suppressed PPARα signaling complex (PPARα / GW6471 / SMRT) and was compared against the activated PPARα complex which included binding of PPARα with the agonist GW409544 and the co-activator, steroid receptor coactivator-1 (SRC-1).
Binding to PPAR alpha is implied given observations of inhibited PPAR alpha nuclear signaling inhibition by nitrotoluenes (Wilbanks et al 2014).
There is no evidence text for this event.
GW6471 is a pharmaceutical developed for human diabetes research. GW6471 was designed specifically to inhibit PPAR alpha signaling (Xu et al 2002).
Characterization of Exposure
GW6471 was administered in biochemical and cell-free assays (Xu et al 2002).
Xu HE, Stanley TB, Montana VG, Lambert MH, Shearer BG, Cobb JE, McKee DD, Galardi CM, Plunket KD, Nolte RT et al: Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPAR[alpha]. Nature 2002, 415(6873):813-817.