LXR623

LXR-β,LXR-α

422.78

DMSO: ≥ 47 mg/mL

Powder

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.

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.

WAY-252623; LXR623; LXR 623; WAY252623; WAY 252623

C₂₁H₁₂ClF₅N₂

875787-07-8