LXR-623 is a brain-penetrant partial LXRα and full LXRβ agonist, with IC₅₀s of 24 nM and 179 nM, respectively.

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. LXR-623 treatment of human PBMC in vitro significantly increases transcription of ABCA1 and ABCG1^[4].

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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. LXR-623 (1.5, 5 mg/kg/day) significantly reduces progression of atherosclerosis in animals compared with the placebo group. 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. 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].

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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. LXR-623 (1.5, 5 mg/kg/day) significantly reduces progression of atherosclerosis in animals compared with the placebo group. 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. 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].

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . 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.  [Content Brief]

  . 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.  [Content Brief]

  . 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.  [Content Brief]

  [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.  [Content Brief]