Evacetrapib (LY2484595)
(Synonyms: 反式-4-[[(5S)-5-[[[3,5-双(三氟甲基)苯基]甲基](2-甲基-2H-四氮唑-5-基)氨基]-2,3,4,5-四氢-7,9-二甲基-1H-1-苯并氮杂卓-1-基]甲基]环己烷羧酸,LY2484595) 目录号 : GC14061
A CETP inhibitor
Cas No.:1186486-62-3
Sample solution is provided at 25 µL, 10mM.
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Evacetrapib is a potent and selective inhibitor of cholesteryl ester transfer protein (CETP) with IC50 value of 5.5nM [1].
As a benzazepine-based inhibitor of CETP, evacetrapib is developed to increase HDL cholesterol for the treatment of coronary artery disease. Evacetrapib is efficacious both in vitro and in vivo. The IC50 values of evacetrapib against CETP are 5.5nM and 26nM, respectively in the buffer assay using human recombinant CETP and in the plasma assay using human plasma CETP. In the animal model of human CETP/ApoAI double transgenic mouse line, oral administration of evacetrapib at 30mg/kg significantly inhibits the CETP activity as well as increases the level of HDL. Besides that, the ED50 value of evacetrapib is less than 5mg/kg. Compared to the previous inhibitors of CETP, evacetrapib has less side effects. It is found no to increase blood pressure Zucker diabetic fatty rats and not to induce aldosterone or cortisol synthesis in H295R cells [1].
References:
[1] Cao G, Beyer TP, Zhang Y, Schmidt RJ, Chen YQ, Cockerham SL, Zimmerman KM, Karathanasis SK, Cannady EA, Fields T, Mantlo NB. Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure. J Lipid Res. 2011 Dec;52(12):2169-76.
Kinase experiment: | Human CETP cDNA is amplified from a human liver cDNA library and the sequence is confirmed to be identical to the published sequence. The cDNA is subcloned into a pcDNA3.1 vector, under the control of CMV promoter. A stable line is established in CV1 cells in which the above-mentioned construct is used to express the recombinant human CETP. The medium contained the secreted recombinant CETP protein and the amount (19 ng/μL) is quantified by an ELISA kit. The medium is then aliquoted in 0.2% BSA and stored at -80°C. The stock CETP protein is diluted 150-fold in CETP buffer (10 mM Tris, 150 mM NaCl, and 2 mM EDTA) before use. The assay is set up in a 96-well plate. Each well received 97.5 μL diluted CETP protein (final concentration 7 nM) and 2.5 μL of compound stock. After a 30 min incubation at 37°C, 5 μL of substrate stock (the same stock used in the human plasma CETP assay), 0.16 μL of VLDL stock (2.5 mg/mL, Intracel) and 145 μL of CETP buffer are added, and the incubation is continued for another 4 h. Signal is read for the human plasma CETP assay[1]. |
Animal experiment: | Rats[1] The blood pressure study is carried out using telemetered, male, obese Zucker Diabetic rats (ZDF fa/fa rats, 8 weeks of age on arrival; n=4). All rats underwent surgical implantation of a telemetry transmitter for continuous monitoring of hemodynamic parameters throughout the study. The rats are acclimated on Purina 5008 chow and house water ad libitum until 11 weeks of age. Mean daily blood pressure for the 24-h period immediately prior to administration of compound is taken as the baseline blood pressure. On the day of an experiment, a single 160 mg/kg dose (in 10% acacia) of Evacetrapib as the lysine salt is administered by oral gavage, and the drug effect is taken as the average daily mean arterial pressure (MAP) during the 24 h period following the dose. Data are expressed as the change in MAP from baseline. Following the last day of blood pressure monitoring, samples are collected from the orbital sinus at 1, 2, 4, 8, and 24 h post dose into tubes containing EDTA and processed into plasma. Plasma concentrations of Evacetrapib are measured using liquid chromatography tandem mass spectrometry. |
References: [1]. Cao G, et al. Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure. J Lipid Res. 2011 Dec;52(12):2169-76. | |
| Cas No. | 1186486-62-3 | SDF | |
| 别名 | 反式-4-[[(5S)-5-[[[3,5-双(三氟甲基)苯基]甲基](2-甲基-2H-四氮唑-5-基)氨基]-2,3,4,5-四氢-7,9-二甲基-1H-1-苯并氮杂卓-1-基]甲基]环己烷羧酸,LY2484595 | ||
| 化学名 | 4-[[(5S)-5-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-7,9-dimethyl-2,3,4,5-tetrahydro-1-benzazepin-1-yl]methyl]cyclohexane-1-carboxylic acid | ||
| Canonical SMILES | CC1=CC(=C2C(=C1)C(CCCN2CC3CCC(CC3)C(=O)O)N(CC4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F)C5=NN(N=N5)C)C | ||
| 分子式 | C31H36F6N6O2 | 分子量 | 638.65 |
| 溶解度 | ≥ 32.1 mg/mL in DMSO, ≥ 50.4 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5658 mL | 7.829 mL | 15.658 mL |
| 5 mM | 0.3132 mL | 1.5658 mL | 3.1316 mL |
| 10 mM | 0.1566 mL | 0.7829 mL | 1.5658 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet