LSZ-102-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELSZ-102Cat. No.: HY-111486CAS No.: 2135600-76-7分式: CHFOS分量: 470.46作靶点: Estrogen Receptor/ERR作通路: Others储存式: -20C, stored under nitrogen* In solvent : -80C, 6 months; -20C, 1 month (stored undernitrogen)溶解性数据体外实验 DMSO : 100 mg/mL

2、 (212.56 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 1.67 mg/mL (3.55 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1.67 mg/mL (3.55 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 1.67 mg/mL (3.55 mM); Clear solution1/2

3、Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 LSZ-102种强效, 服物有效的选择性雌激素受体降解剂, 其 IC50 值为 0.2 nM。IC50 & Target estrogen receptor 1体外研究 LSZ-102 is a potent, orally bioavailable selective estrogen receptor degrader with an IC50 of 0.2 nM andcurrently in Phase I/Ib trials for the trea

4、tment of ER positive breast cancer. LSZ-102 induces significantdegradation of ER after 24 h, when given as a 10 M solution to MCF-7 cells. Robust inhibition of cellproliferation in MCF-7 cells is observed upon incubation with LSZ-102 with a half inhibitory concentration of1.7 nM. Results demonstrate

5、 that LSZ-102 effectively inhibits the estrogen-induced activation of the ERE-luciferase reporter using charcoal-stripped serum treated with E2 with IC50 of 0.3 nM 1.体内研究 Treatment of the mice with LSZ-102 once daily at 20 mg/kg results in significant tumor growth inhibition ascompare to the control

6、 group treated with vehicle alone, resulting in tumor stasis (mean change in tumorvolume of LSZ-102 vs control=%T/C of 2.4% on day 48, p 1.PROTOCOLKinase Assay 1 Growth factors depleted MCF-7 ERE-luc cells are used and seeded (10 000 cells/well) in 96-well plates inCSS medium. After overnight incuba

7、tion, cells are treated with LSZ-102 in the presence of estradiol (0.1 nM)for 24 h. Cells are then lysed and quantified for luciferase activity using Bright-Glo assay 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Female athymic nude mice are

8、used for tumor xenograft studies. MCF-7 cells are subcutaneously injectedAdministration 1 (200 L/animal) in the right axillary mammary fat pad area. Tumor volume and body weights are measuredtwice weekly. When tumors reach an average volume of 200 mm3, mice are randomized into differentgroups. Anima

9、ls are orally administered vehicle alone or 20 mg/kg LSZ-102 daily or 60 mg/kg tamoxifen 5days per week 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Tria GS, et al. Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment ofEstrogen Receptor Positive Breast Cancer. J Med Chem. 2018 Apr 12;61(7):2837-2864.McePdfHeightCaution: Product has not been fully validated for