GW3965

Agonist of NR1H2, NR1H3

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 ratings)

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.

Information

NR1H2
NR1H3

Agonist

Probe Availability:

In Vitro Validations

Uniprot ID: P55055

Target Class: NHR

Target SubClass: NR1 Subfamily

Potency: IC 50

Potency Value: 125 nM

Potency Assay: LXRalpha/SRC1 LiSA.

PDB ID for probe-target interaction (3D structure): --

Structure-activity relationship: Yes some, see J Med Chem paper.

Target aliases:

Oxysterols receptor LXR-beta, UNR, NER, LXRB, NR1H ...

DOI Reference: 10.1021/jm0255116

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): In a panel of nuclear receptors, GW3965 was only active against LXR and PXR. Panel included: PPARalpha, PPARdelta, PPARgamma, FXR, LXRalpha, LXRbeta, RARalpha, TRbeta, VDR, CAR, AR, GR, MR and PR). In GAL4-reporter assay, GW3965 was >10-fold selective for LXR>PXR.

Probe Selectivity in Vitro:

In a panel of nuclear receptors, GW3965 was only active against LXR and PXR. The panel included: PPARalpha, PPARdelta, PPARgamma, FXR, LXRalpha, LXRbeta, RARalpha, TRbeta, VDR, CAR, AR, GR, MR and PR). In GAL4-reporter assay, GW3965 was >10-fold selective for LXR>PXR.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

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 more potent in agonizing the LXRs in cells but suffers from the liability of activity at a handful of other nuclear receptors, notably PXR. GW3965 has properties amenable for in vivo usage.

(last updated: 4 Aug 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

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 for the community to report new findings using this probe to fully validate its applicability.

(last updated: 11 Aug 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

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 orthogonal tool is LXR-623, which could be used in parallel to confirm outcomes.

(last updated: 18 Aug 2017 )

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)