LXR-623

Catalog No.S8390 Batch:S839001

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Technical Data

Formula

C21H12ClF5N2
Molecular Weight 422.78 CAS No. 875787-07-8
Solubility (25°C)* In vitro DMSO 84 mg/mL (198.68 mM)
Ethanol 84 mg/mL (198.68 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description LXR-623 is a novel liver X-receptor(LXR) agonist with IC50 values of 179 nM and 24 nM for LXR-α and LXR-β, respectively. It is orally bioavailable and readily passes the blood-brain barrier.
Targets
LXR-β [1] LXR-α [1]
24 nM 179 nM
In vitro LXR-623 suppresses LDLR expression, increases expression of the ABCA1 efflux transporter, and induces substantial cell death in all of the GBM samples tested. The brain metastatic breast cancer cell line MDA-MB-361, which harbors ERBB2 amplification, is also highly sensitive to LXR-623- dependent cell death in a concentration-dependent manner. LXR-623 inhibits LDL uptake and induces cholesterol efflux in GBM cells, resulting in a significant reduction in cellular cholesterol content. Normal brain cell insensitivity to LXR-623 may be due to reliance on endogenous synthesis of cholesterol and intact negative feedback through synthesis of endogenous oxysterols[3].
In vivo LXR-623 is absorbed rapidly with peak concentrations (Cmax) achieved at approximately 2 hours. The Cmax and area under the concentration-time curve increases in a dose-proportional manner. The mean terminal disposition half-life is between 41 and 43 hours independently of dose. In a low-density lipoprotein (LDL) receptor, (LDLr) knockout mouse model of atherosclerosis, LXR-623 administered orally upregulates intestinal ABCG5 and ABCG8 and reduces atheroma burden without altering serum or hepatic cholesterol and trig-lycerides. LXR-623 shows brain penetration and causes tumor regression in a GBM(glioblastomas) mouse model, reducing cholesterol and inducing cell death[1].

Protocol (from reference)

Cell Assay:[2]
  • Cell lines

    Human PBMC

  • Concentrations

    2 μM

  • Incubation Time

    18 h

  • Method

    The purified PBMC are resuspended in culture medium (RPMI + 10% fetal calf serum + 1% penicillin/streptomycin with 1% L-glutamine), transferred to 6-well (9.5 cm2 each) tissue culture dishes at approximately 5 × 106 cells per well, and 2 μM LXR-623 or vehicle (DMSO) are added. After 18 hours of culture, RNA isolation and qPCR analysis for LXRα, LXRβ, ABCA1, ABCG1, and PLTP is performed.
Animal Study:[2]
  • Animal Models

    C57/Bl6 mice

  • Dosages

    30 mg/kg

  • Administration

    oral administration

Selleck's LXR-623 has been cited by 4 publications

Liver X receptor-agonist treatment rescues degeneration in a Drosophila model of hereditary spastic paraplegia [ Acta Neuropathol Commun, 2022, 10(1):40] PubMed: 35346366
Lipoprotein Deprivation Reveals a Cholesterol-Dependent Therapeutic Vulnerability in Diffuse Glioma Metabolism [ Cancers (Basel), 2022, 14(16)3873] PubMed: 36010867
Activation of LXRβ inhibits tumor respiration and is synthetically lethal with Bcl-xL inhibition. [ EMBO Mol Med, 2019, 11(10):e10769] PubMed: 31468706
Activation of LXR Receptors and Inhibition of TRAP1 Causes Synthetic Lethality in Solid Tumors. [ Cancers (Basel), 2019, 11(6)] PubMed: 31181660

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.