| Bioactivity | LXR-623 is a brain-penetrant partial LXRα and full LXRβ agonist, with IC50s of 24 nM and 179 nM, respectively. | ||||||||||||
| Target | IC50: 24 nM (LXR-α), 179 nM (LXR-β) | ||||||||||||
| Invitro | 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. LXR-623 suppresses LDLR expression, increases expression of the ABCA1 efflux transporter, and induces substantial cell death in all of the GBM samples tested. LXR-623 (5 μM) also induces GBM cell death through activation of LXRβ[1]. LXR-623 treatment of human PBMC in vitro significantly increases transcription of ABCA1 and ABCG1[4]. | ||||||||||||
| In Vivo | LXR-623 (400 mg/kg, p.o.) 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. LXR-623 inhibits tumor growth, promotes tumor cell death, and prolongs the survival of mice bearing intracranial patient-derived GBMs[1]. LXR-623 (1.5, 5 mg/kg/day) significantly reduces progression of atherosclerosis in animals compared with the placebo group[2]. WAY-252623 (15 and 50 mg/kg) results in a significant reduction of atherosclerosis in a dose-dependent manner. WAY-252623 (20, 60, and 120 mg/kg/day, p.o.) displays neutral lipid effects in this CETP-expressing Syrian hamster[3]. Moreover, LXR-623 (50 mg/kg) induces gene expression in rodent peripheral blood cells in rat. LXR-623 (0, 15 and 50 mg/kg) dose-dependently upregulates transcription of ABCA1 and ABCG1 in monkey whole blood cells proportional to dose[4]. | ||||||||||||
| Name | LXR-623 | ||||||||||||
| CAS | 875787-07-8 | ||||||||||||
| Formula | C21H12ClF5N2 | ||||||||||||
| Molar Mass | 422.78 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [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. |