GW7647

GW7647 : Agonist of PPARA

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

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Probe GW7647 is in the process of SERP review.

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Information

PPARA

Agonist

up to 1 uM

Probe Availability:

In Vitro Validations

Uniprot ID: Q07869

Target Class: Nuclear Hormone Receptor

Target SubClass: Nuclear receptor 1C1

Potency: EC50

Potency Value: 6 nM

Potency Assay: Activity on the human PPAR subtypes in vitro

PDB ID for probe-target interaction (3D structure): 6DRG, 6KAY, 6KB3, 6KB8, 7BQ3

Target aliases:

Peroxisome proliferator-activated receptor alpha, ...

DOI Reference: 10.1016/S0960-894X(01)00188-3

Uniprot ID: Q07869

Target Class: Nuclear Hormone Receptor

Target SubClass: Nuclear receptor 1C1

Potency: EC50

Potency Value: 51.8 nM

Potency Assay: PPARA activation TR-FRET

PDB ID for probe-target interaction (3D structure): 6DRG, 6KAY, 6KB3, 6KB8, 7BQ3

Target aliases:

Peroxisome proliferator-activated receptor alpha, ...

DOI Reference: 10.1016/j.isci.2020.101727

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): Selectivity >100-fold over PPARγ and PPARδ EC50 1100 nM PPARγ EC50 6200 nM PPARδ

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This is perhaps the most selective agonist for PPARa and is potent and efficacious both in vitro and in vivo. The compound is orally bioavailable in rat with dose promotional exposure at 1 and 10 mg/kg but PK details are not available. No off-target screen has been published.

(last updated: 22 Nov 2022 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This probe shows high selectivity for PPARa using cell-based reporter assays for PPARs alpha/beta/gamma, and in vivo studies using multiple species (rat, hamster) have demonstrated expected alterations to lipid levels. While fibrate drugs elicit effects in part via PPARa, this more elaborated PPARa modulator may offer greater target selectivity. However, cell-based PPARa-dependent phenotypes beyond reporter assays are scarce, and the high logP of the structure suggests that significant off-target effects beyond the PPAR class are likely. Additionally, as far as I see no clear PK data have been presented that might guide dose selection beyond the published reports that efficacy is observed in rats/hamsters at 3 and 10 mpk.

(last updated: 1 Dec 2022 )