LY2562175
目录号 : GC19421
An FXR agonist
Cas No.:1103500-20-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | LY2562175 is tested in concentration-response curves by an FXR-SRC-1 Cofactor Recruitment assay using the Alpha Screen technology according to the manufacturer instructions. Briefly, purified 6-HIS-tagged human FXR ligand-binding domain (amino acids 242-472), purified GST-tagged human SRC-1 nuclear receptor-interacting domain (amino acids 220-394), Nickel Chelate donor beads and Anti-GST antibody acceptor beads are mixed together and 12 μL per well is aliquoted into 384 well plates. Add LY2562175 in 3 μL per well for a total assay volume of 15 μL and incubate at room temperature in the dark for 4 hours. After incubation, LY2562175 that binds FXR and induces the interaction between the FXR and SRC-1 will bring the two bead types into proximity generating luminescence that is quantified using a Packard Fusion instrument. Calculate EC50 values for LY2562175[1]. |
Animal experiment: | To assess the potency and efficacy of LY2562175 in vivo, studies are conducted in 8 week old, male LDLR null mice fed a “Western” diet. Animals are allowed to acclimate to the high fat/high cholesterol chow TD88137 (containing 0.15% cholesterol and 42% fat) for 2 weeks prior to the study. Animals are divided into groups of six and dosed once daily for 1 week by gavage with solutions of LY2562175 in situ sodium salt or with vehicle (5% Solutol, 5% EtOH, 1 wt %/v CMC) at a dose volume of 5 mL/kg. On the seventh day, animals are bled by cardiac puncture under anesthesia with CO2. Serum is prepared from individual animals for determination of cholesterol and triglycerides by enzymatic analysis. Pooled samples from each treatment group are used for determination of lipoprotein subtypes. ED50 values (dose producing half-maximal effect) for the decrease in serum cholesterol and triglycerides are determined by nonlinear regression analysis[1]. |
References: [1]. Genin MJ, et al. Discovery of 6-(4-{[5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl]methoxy}piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic Acid: A Novel FXR Agonist for the Treatment of Dyslipidemia. J Med Chem. 2015 Dec 24;58(24):9768-72. | |
LY2562175 is a potent and selective FXR agonist with an EC50 of 193 nM.
LY2562175 promotes transcriptional activation of human FXR in a cell-based co-transfection assay with an EC50 of 193 nM. LY2562175 promotes recruitment of a peptide from the nuclear receptor interaction domain of the coactivator SRC-1 with a relative EC50 of 121 nM and 93.5% efficacy as compare to GW4064[1].
LY2562175 causes a dose-dependent decrease in serum cholesterol and serum triglycerides. At a dose of 10 mg/kg, the decrease in cholesterol with LY2562175 is 80% below vehicle-treated animals, and the decrease in serum triglycerides is 76% from control group. The ED50 for serum cholesterol is determined to be 2 and 3.4 mg/kg for serum triglycerides. Treatment of female ZDF rats with LY2562175 results in a dose dependent lowering of plasma triglycerides in the fasted and nonfasted states. When administered as a fixed dose combination with rosiglitazone, LY2562175 further lowers fasted and nonfasted plasma triglycerides. FPLC fractionation of the lipoproteins reveals that LY2562175 treatment results in a reduction in vLDL-C and a dramatic increase in HDL-c in this animal model[1].
Reference
[1]. Genin MJ, et al. Discovery of 6-(4-{[5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl]methoxy}piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic Acid: A Novel FXR Agonist for the Treatment of Dyslipidemia. J Med Chem. 2015 Dec 24;58(24):9768-72.
| Cas No. | 1103500-20-4 | SDF | |
| Canonical SMILES | O=C(C1=CN(C)C2=C1C=CC(N3CCC(OCC4=C(C5CC5)ON=C4C6=C(Cl)C=CC=C6Cl)CC3)=C2)O | ||
| 分子式 | C28H27Cl2N3O4 | 分子量 | 540.44 |
| 溶解度 | DMF: 20 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:3): 0.25 mg/ml | 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 | 1.8503 mL | 9.2517 mL | 18.5034 mL |
| 5 mM | 0.3701 mL | 1.8503 mL | 3.7007 mL |
| 10 mM | 0.185 mL | 0.9252 mL | 1.8503 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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