LXR-623

製品コードS8390 バッチS839001

印刷

化学情報

Chemical Structure Synonyms WAY-252623 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C21H12ClF5N2
分子量 422.78 CAS No. 875787-07-8
Solubility (25°C)* 体外 DMSO 84 mg/mL (198.68 mM)
Ethanol 84 mg/mL warmed with 50ºC water bath (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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 Human PBMC
濃度 2 μM
反応時間 18 h
実験の流れ 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.
動物実験 動物モデル C57/Bl6 mice
投薬量 30 mg/kg
投与方法 oral administration

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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