SR9243

Inverse Agonist of NR1H2, NR1H3

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

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Probe SR9243 is in the process of SERP review.

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Information

NR1H2
NR1H3

Inverse Agonist

up to 1 uM

Probe Availability:

In Vitro Validations

No in Vitro Validations

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Cell:

Specificity of SR9243 was illustrated in a cell-based co-transfection assay with 46 nuclear receptors in a Gal4-NR LBD panel.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 7 Jan 2022 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This LXR inverse agonist offers activity across a range of cell-based LXR assays, typically with EC50 values in the mid-nanomolar range. Additionally, cancer cell killing was observed, in some cases with higher potency. Selectivity vs a wide range of nuclear receptors was established at 10 uM. However, the large size and high hydrophobicity of the probe suggests potential for off-target interactions. IP injections at 30 or 60 mpk led to changes in various metabolic parameters, and antitumor effects were also seen. No PK data was presented to rationalize those dose choices, and no information regarding CNS penetrance was presented. Improves on the related SR9238 by removing the labile ester group to improve systemic exposure. Overall, likely the best available choice for antagonizing LXR function in cells and in vivo.

(last updated: 13 Jan 2022 )