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GW3965 | Agonist of NR1H2, NR1H3
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
NR1H2
  • IC 50:125 nM
  • EC 50:190 nM
NR1H3
  • EC50:125 nM
  • EC 50:30 nM
Agonist
100 nM - 1 uM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
In a panel of nuclear receptors, GW3965 was only active against LXR and PXR. Panel included: PPARalp ...
Selectivity Assessment Description:
In a panel of nuclear receptors, GW3965 was only active against LXR and PXR. The panel included: PPA ...

Potency
Cellular
In Vitro

NR1H2

Mode of Action: Agonist

Structure-Activity-Relationship data available? No

DOI Reference: 10.1021/jm0255116

NR1H3

Mode of Action: Agonist

Structure-Activity-Relationship data available? No

DOI Reference: 10.1021/jm0255116

In Vivo Validations

Mouse
Dose: 10 mg/kg
Route of delivery: Oral
Plasma half life: 2 h
Organ of interest (O): Plasma, small intestine, peripheral macrophages
Target engagement assay: Indirect: In small intenstine and peripheral macrophages, GW3965 increased ABCA1 7-8 fold. In plasma, GW3965 increased HDL cholesterol 30%.

DOI Reference: 10.1021/jm0255116

Orthogonal Probes def

T0901317
LXR-623

Chemical Information

Molecular Formula C33H31ClF3NO3
SMILEs O=C(O)Cc1cccc(OCCCN(Cc2cccc(C(F)(F)F)c2Cl)CC(c2ccccc2)c2ccccc2)c1
InChI InChI=1S/C33H31ClF3NO3/c34-32-27(15-8-17-30(32)33(35,36)37)22-38(18-9-19-41-28-16-7-10-24(20-28)21-31(39)40)23-29(25-11-3-1-4-12-25)26-13-5-2-6-14-26/h1-8,10-17,20,29H,9,18-19,21-23H2,(H,39,40)
Molecular weight 581.19 Da
AlogP 8.0891
HBond acceptors 4
HBond donors 1
Atoms 72

Vendors

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Expert Reviews

by SERP
(on 4 Aug 2017 )
Cellular Use Rating
In Model Organisms
GW3965 has been widely used as a chemical probe for the liver X receptors, alpha and beta. GW3965 is commonly employed in parallel with another LXR agonist such as T1317. T1317 is approximately 10-fold...
by SERP
(on 11 Aug 2017 )
Cellular Use Rating
In Model Organisms
This appears to be a robust and credible probe for the investigation of LXR biology, though the primary literature reference is somewhat sparse in terms of utilization and limitation. It will be important...
by SERP
(on 18 Aug 2017 )
Cellular Use Rating
In Model Organisms
GW3965 is a selective non-steroidal agonist for the LXRa and LXRb receptors. GW3965 is suitable for in vivo use in mouse models where a 10mg/kg oral dose exceeds the LXR EC50. A complementary, structurally...

Portal Comments

A 2020 publication shows that T0901317 exert unspecific effects on pancreatic β-cell function DOI: 10.1007/s12020-020-02241-4

(last updated: 9 Jul 2020)

Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria