T0901317

Protein target name:

NR1H3, NR1H2

Mechanism of action:

Agonist

Recommended Concentration for use in cells:

~~5 -10 uM~~

Reviewer suggested Concentration for use in cells:

up to 1 uM

Probe Availability

Abcam (293754-55-9)

MedChemExpress

TOCRIS

Probe Information

Target and Probe Information

Target Details

Target class:

Other

Define other target class:

Hormone Nuclear Receptor

Subclass:

NR1 Subfamily

HUGO ID:

HGNC:7965 HGNC:7966

Entrez gene ID:

7376 10062

UNIPROT ID:

P55055 Q13133

Target alias:

NR1H2, LXR-b, LXRB, NER, NER-I, RIP15, UNR, NR1H3, LXR-a, LXRA, RLD-1, LXR-alpha, LXR-beta

Probe Details

Chemical Probes Portal ID:

CPP1751

Probe alias:

T 0901317; TO-901317; TO901317

PubChem CID:

447912

ChEMBL ID:

CHEMBL62136

SMILES string:

C1=CC=C(C=C1)S(=O)(=O)N(CC(F)(F)F)C2=CC=C(C=C2)C(C(F)(F)F)(C(F)(F)F)O

InChi Key:

SGIWFELWJPNFDH-UHFFFAOYSA-N

Orthogonal probe:

GW3965

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

LXR-alpha 20 nM, 10 nM LXR-alpha and 8 nM LXR-beta

Potency assay:

Scintillation proximity assay, FRET-based co-activator (SRC-1) recruitment assay measuring agonist activity

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

1PQC

Structure-activity relationship:

Available through the years in multiple papers.

Off target activity

Probe Selectivity in Vitro:

In a panel of hormone receptors, 10 uM T0901317 showed activity against LXR-alpha>LXR-beta>PXR and no activity against other receptors (FXR, RXRalpha, PPARalpha, PPARdelta, PPARgamma, CAR, ERRalpha, CPF, HNF4alpha, RORalpha, Nor1, Nurf1, COUPTFII, RORg (204 nM)

In cell validation

On target activity in cells

Potency in cells:

EC50

85 nM LXR apha75 nM LXR beta

Potency assay (cells):

Cell-based reporter gene assay

Off target activity in cells

Potency assay, off target (cells):

In vivo validation

Organism:

C57BL/6 mice

Dose:

10 mg/Kg PO20 mg/Kg IP50 mg/Kg IP

Route of delivery:

OralIntraperitoneal

Plasma half life:

4.9 (S), 3.3 (L), 4.5 (B) h

Cmax:

720 (S), 4334 (L), 2029 (B) ug/L

Tmax:

1.5 (S), 1.5 (L), 4.0 (B) h

Organ of Interest

Organ (O):

Serum LiverBrain

Target engagement assay:

T0901317 increased plasma triglycerides and HDL cholesterol.

Primary Reference

Reference (doi):

10.1126/science.289.5484.1524 10.1101/gad.850400 10.1016/j.bmcl.2009.02.039 10.1016/j.jpba.2020.113420

Reference (PMID):

10968783 11090131 19264481 32593849

External Resources

Available data:

GDSC

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells and in model organisms.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

Jul 9 2020 - 12:55pm

Probe is highly specific for LXR amongst all steroid hormone receptors tested. Agonist is able to activate LXR target genes and reporters in cell lines and in mice.

Sep 15 2020 - 8:29am

T 0901317 is a widely used chemical probe for LXRa/LXRb. It has good potency and selectivity across the nuclear hormone receptor family if used at the appropriate concentrations (maximum 1uM in cells). At high micromolar concentrations, cross-reactivity has been noted on RORa doi: 10.1124/mol.109.060905. T 0901317 can be used as an in vivo chemical probe by oral administration in mice and rats.

Nov 4 2020 - 1:39pm

T0901317 is a selective probe for LXRα and LXRβ. Although there is no data for selectivity outside of the target family, selectivity across the nuclear hormone receptor family is good within appropriate concentrations (see RORα/γ as exceptions). The probe may also exert acute effects nongenomic in nature and alterations in β-Cell function should be considered at higher concentrations, DOI: 10.1210/en.2016-1941.

May 4 2021 - 1:38pm

T0901317

Probe Availability

Probe Information

Target Details

NR1H2, LXR-b, LXRB, NER, NER-I, RIP15, UNR, NR1H3, LXR-a, LXRA, RLD-1, LXR-alpha, LXR-beta

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

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T0901317

Probe Availability

Probe Information

Target Details

NR1H2, LXR-b, LXRB, NER, NER-I, RIP15, UNR, NR1H3, LXR-a, LXRA, RLD-1, LXR-alpha, LXR-beta

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?