Evacetrapib-LY2484595-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEEvacetrapibCat. No.: HY-13327CAS No.: 1186486-62-3Synonyms: LY2484595分式: CHFNO分量: 638.65作靶點: CETP作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (156

2、.58 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.91 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (3.91 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Evacetrapib種有效的選擇性的 CETP 抑制劑，在漿中，抑制重 組 CETP 蛋 (IC50 為

3、 5.5 nM) 和CETP 活性，IC50 為 36 nM。IC50 & Target IC50: 5.5 nM (CETP) 1體外研究 Evacetrapib is a novel benzazepine-based CETP inhibitor. In the buffer CETP assay, the absolute potency ofthe compound is 5.5 nM. In the human plasma CETP assay, the CETP concentration is about 2 g/mL (25nM) and the 36 nM IC50 va

4、lue again indicates that Evacetrapib is a potent CETP inhibitor against either therecombinant protein or CETP from human plasma. Evacetrapib is apparently much more potent thanDalcetrapib 1.體內(nèi)研究 In double transgenic mice expressing human CETP and apoAI, Evacetrapib exhibits an ex vivo CETPinhibition

5、 ED50 of less than 5 mg/kg at 8 h post oral dose and significantly elevated HDL cholesterol.Importantly, no blood pressure elevation is observed in rats dosed with Evacetrapib at high exposuremultiples compared with the positive control, torcetrapib. Evacetrapib administered orally at 30 mg/kg resul

6、tsin 98.4%, 98.6%, and 18.4% inhibition of CETP activity at 4, 8 and 24 h post dose respectively. Evacetrapibdosed orally at 30 mg/kg resulted in 129.7% increase in HDL-C 8 h after oral administration 1.PROTOCOLKinase Assay 1 Human CETP cDNA is amplified from a human liver cDNA library and the seque

7、nce is confirmed to beidentical to the published sequence. The cDNA is subcloned into a pcDNA3.1 vector, under the control ofCMV promoter. A stable line is established in CV1 cells in which the above-mentioned construct is used toexpress the recombinant human CETP. The medium contained the secreted

8、recombinant CETP protein andthe amount (19 ng/L) is quantified by an ELISA kit. The medium is then aliquoted in 0.2% BSA and stored at-80C. The stock CETP protein is diluted 150-fold in CETP buffer (10 mM Tris, 150 mM NaCl, and 2 mMEDTA) before use. The assay is set up in a 96-well plate. Each well

9、received 97.5 L diluted CETP protein(final concentration 7 nM) and 2.5 L of compound stock. After a 30 min incubation at 37C, 5 L of substratestock (the same stock used in the human plasma CETP assay), 0.16 L of VLDL stock (2.5 mg/mL, Intracel)and 145 L of CETP buffer are added, and the incubation i

10、s continued for another 4 h. Signal is read for thehuman plasma CETP assay 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 1Administration 1 The blood pressure study is carried out using telemetered, male, obese Zucker Diabetic rats (ZDF f

11、a/fa rats,8 weeks of age on arrival; n=4). All rats underwent surgical implantation of a telemetry transmitter forcontinuous monitoring of hemodynamic parameters throughout the study. The rats are acclimated on Purina5008 chow and house water ad libitum until 11 weeks of age. Mean daily blood pressu

12、re for the 24-h period2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEimmediately prior to administration of compound is taken as the baseline blood pressure. On the day of anexperiment, a single 160 mg/kg dose (in 10% acacia) of Evacetrapib as the lysine salt is administered by oralgavage, and the

13、 drug effect is taken as the average daily mean arterial pressure (MAP) during the 24 hperiod following the dose. Data are expressed as the change in MAP from baseline. Following the last day ofblood pressure monitoring, samples are collected from the orbital sinus at 1, 2, 4, 8, and 24 h post dose

14、intotubes containing EDTA and processed into plasma. Plasma concentrations of Evacetrapib are measuredusing liquid chromatography tandem mass spectrometry.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Atherosclerosis. 2014 Aug;235(2):449-6

15、2. PLoS One. 2017 Aug 2;12(8):e0180772.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Cao G, et al. Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterolwithout inducing aldosterone or increasing blood pressure. J Lipid Res.