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Purity: ≥98%
LXR623 (WAY-252623; LXR-623) is a novel, highly brain-penetrant, selective and orally bioavailable synthetic modulator of LXR (Liver X receptor) with anticancer activity, It is a partial LXRα and full LXRβ agonist with IC50s of 24 nM and 179 nM, respectively. As a LXRα-partial/LXRβ-full agonist, LXR623 selectively kills GBM cells in an LXRβ- and cholesterol-dependent fashion, causing tumor regression and prolonged survival in mouse models. LXR623 displayed high efficacy in reducing lesion progression in the murine LDLR(-/-) atherosclerosis model with no associated increase in hepatic lipogenesis either in this model or Syrian hamsters. LXR-623 potently kills U87EGFRvIII and GBM39 cells in vitro while completely sparing NHAs. LXR-623 also increases ABCA1 protein and decreases LDLR protein levels in all three cell lines.
| ln Vitro |
In vitro, LXR-623 completely protects NHA while killing U87EGFRvIII and GBM39 cells efficiently. In all three cell lines, LXR-623 also caused an increase in ABCA1 protein and a decrease in LDLR protein levels. In every GBM sample examined, LXR-623 caused massive cell death, upregulated the expression of the ABCA1 efflux transporter, and inhibited the expression of LDLR. By activating LXRβ, LXR-623 (5 μM) also causes GBM cell death[1]. When human PBMCs were treated with LXR-623 in vitro, the transcription of ABCA1 and ABCG1 was markedly elevated [4].
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| ln Vivo |
With little peripheral activity, LXR-623 (400 mg/kg, po) penetrates the blood-brain barrier, triggers the expression of the target gene, and reaches processing levels in GBM cells in the brain. LXR-623 prolongs the survival of mice with intracranial patient-derived GBMs by suppressing tumor growth and promoting tumor cell death [1]. When compared to a placebo, LXR-623 (1.5, 5 mg/kg/day) dramatically slowed the advancement of atherosclerosis in animals [2]. A dose-dependent manner was observed in the significant reduction of atherosclerosis by WAY-252623 (15 and 50 mg/kg). In Syrian hamsters that express CETP, WAY-252623 (20, 60, and 120 mg/kg/day, po) exhibits neutral lipid effects [3]. Additionally, rats' peripheral blood cells showed increased gene expression in response to LXR-623 (50 mg/kg). In monkey whole blood cells, LXR-623 (0, 15 and 50 mg/kg) dose-dependently and proportionately increases the transcription of ABCA1 and ABCG1 [4].
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| References |
[1]. Villa GR, et al. An LXR-Cholesterol Axis Creates a Metabolic Co-Dependency for Brain Cancers. Cancer Cell. 2016 Nov 14;30(5):683-693.
[2]. Giannarelli C, et al. Synergistic effect of liver X receptor activation and simvastatin on plaque regression and stabilization: an magnetic resonance imaging study in a model of advanced atherosclerosis. Eur Heart J. 2012 Jan;33(2):264-73. [3]. Quinet EM, et al. LXR ligand lowers LDL cholesterol in primates, is lipid neutral in hamster, and reduces atherosclerosis in mouse. J Lipid Res. 2009 Dec;50(12):2358-70. [4]. DiBlasio-Smith EA, et al. Discovery and implementation of transcriptional biomarkers of synthetic LXR agonists in peripheral blood cells. J Transl Med. 2008 Oct 16;6:59 |
| Molecular Formula |
C21H12CLF5N2
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| Molecular Weight |
422.78
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| CAS # |
875787-07-8
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| SMILES |
ClC1C([H])=C(C([H])=C([H])C=1C([H])([H])N1C(C2C([H])=C([H])C(=C([H])C=2[H])F)=C2C([H])=C([H])C([H])=C(C(F)(F)F)C2=N1)F
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3653 mL | 11.8265 mL | 23.6530 mL | |
| 5 mM | 0.4731 mL | 2.3653 mL | 4.7306 mL | |
| 10 mM | 0.2365 mL | 1.1826 mL | 2.3653 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
LXR-623 crosses the blood brain barrier, induces target gene expression, and achieves therapeutic levels in GBM cells in the brain with minimal activity in the periphery.Cancer Cell.2016 Nov 14;30(5):683-693. |
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 LXR-623 kills GBM cells through activation of LXRβ, the dominant subtype in brain tumors.Cancer Cell.2016 Nov 14;30(5):683-693. |
 LXR-623 inhibits tumor growth, promotes tumor cell death and prolongs the survival of mice bearing intracranial patient-derived GBMs.Cancer Cell.2016 Nov 14;30(5):683-693. |
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