Stressor: 151




Stressor Overview


AOPs Including This Stressor


Events Including This Stressor


Chemical Table


The Chemical Table lists chemicals associated with a stressor. This table contains information about the User’s term for a chemical, the DTXID, Preferred name, CAS number, JChem InChIKey, and Indigo InChIKey.


To add a chemical associated with a particular stressor, next to the Chemical Table click ‘Add chemical.’ This will redirect you to a page entitled “New Stressor Chemical.’ The dialog box can be used to search for chemical by name, CAS number, JChem InChIKey, and Indigo InChIKey. Searching by these fields will bring forward a drop down list of existing stressor chemicals formatted as “CAS- preferred name” “JChem InChIKey – preferred name” or “Indigo InChIKey- preferred name” depending on which field you perform the search. Select an entity from the drop down list and click ‘Add chemical.’ This will return you to the Stressor Page, where the new record should be in the ‘Chemical Table’ on the page.

AOP Evidence


Antagonist binding to PPARα leading to body-weight loss

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).

Event Evidence


Binding as antagonist, Antagonist binding to PPARalpha ligand binding domain

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 of antagonist, PPAR alpha

Binding to PPAR alpha is implied given observations of inhibited PPAR alpha nuclear signaling inhibition by nitrotoluenes (Wilbanks et al 2014). 

stabilization, PPAR alpha co-repressor

There is no evidence text for this event.

Stressor Info


Chemical/Category Description


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.