BMS 687453
目录号 : GC15995
A potent PPARα agonist
Cas No.:1000998-59-3
Sample solution is provided at 25 µL, 10mM.
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IC50: 10 nM for human PPARα
BMS 687453 is a PPARα agonist.
The peroxisome proliferator activated receptor (PPAR) is a member of the intracellular nuclear hormone receptor superfamily of transcription factors, having pleiotropic effects on plasma lipoprotein levels, insulin sensitization, atherosclerosis, and inflammation.
In vitro: BMS-687453 was identified as a potent and selective PPAR alpha agonist, with approximately 410-fold selectivity versus human PPARgamma in PPAR-GAL4 transactivation assays. In addition, similar potency and selectivity were also seen in the full length receptor co-transfection assays. [1].
In vivo: In previous study, BMS-687453 had an excellent pharmacokinetic profile across all tested animal species. The oral absorption was rapid in mouse, rat, dog, and cynomulgus monkey. BMS-687453 also exhibited low plasma clearance in the mouse, rat, and monkey and moderate plasma clearance in the dog. The half-life of BMS-687453 ranged from 3 h in mouse to 12 h in cynomolgus monkeys. BMS-687453 showed excellent absolute oral bioavailability ranging from 58% (dog) to 91% (rat) [1].
Clinical trial: Up to now, BMS 687453 is still in the preclinical development stage.
Reference:
[1] Li J. Discovery of an oxybenzylglycine based peroxisome proliferator activated receptor alpha selective agonist 2-((3-((2-(4-chlorophenyl)-5-methyloxazol-4-yl)methoxy)benzyl)(methoxycarbonyl) amino)acetic acid (BMS-687453). J Med Chem. 2010 Apr 8;53(7):2854-64.
Kinase experiment: | A homogeneous, fluorescent polarization PPARα and PPARγ binding assay is used as the primary screen for determining the PPARα and PPARγ binding affinity of compounds. The human functional activity of PPARα and PPARγ agonists is determined by using the GAL4-LBD assays. The in vitro hamster, rat, and mouse PPARα functional activities are tested in the chimeric GAL4/PPARα assay format. The data are reported as an EC50 value calculated using XLfit 4 parameter fit and floating all parameters. Full length human PPARα and PPARγ co-transfection assays in HepG2 cells are employed for further testing the leading compounds (BMS-687453)[1]. |
Animal experiment: | Male 6−8 week old human apoA1 transgenic mice are randomly assigned into different treatment groups and weighed and dosed by oral gavage (5 mL/kg body weight) once a day in the morning with vehicle alone or with compound (BMS-687453) and allowed free access to food and water. The study duration is 10 days. After dosing on day 10, mice are fasted for 4 h and sacrificed by CO2 asphyxiation, and blood samples are collected in serum-separating tubes via cardiac puncture for lipid measurements. Livers are dissected out, weighed, and quickly frozen in liquid nitrogen for future RNA analysis. Human apoA1 concentration in serum is measured using the apolipoprotein A1 kit[1]. |
References: [1]. Li J, et al. Discovery of an oxybenzylglycine based peroxisome proliferator activated receptor alpha selective agonist 2-((3-((2-(4-chlorophenyl)-5-methyloxazol-4-yl)methoxy)benzyl)(methoxycarbonyl)amino)acetic acid (BMS-687453). J Med Chem. 2010 Apr 8;53(7):2854-64. | |
| Cas No. | 1000998-59-3 | SDF | |
| 化学名 | N-[[3-[[2-(4-chlorophenyl)-5-methyl-4-oxazolyl]methoxy]phenyl]methyl]-N-(methoxycarbonyl)-glycine | ||
| Canonical SMILES | OC(CN(C(OC)=O)CC1=CC(OCC2=C(C)OC(C3=CC=C(Cl)C=C3)=N2)=CC=C1)=O | ||
| 分子式 | C22H21ClN2O6 | 分子量 | 444.9 |
| 溶解度 | DMSO: 30 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 | 2.2477 mL | 11.2385 mL | 22.477 mL |
| 5 mM | 0.4495 mL | 2.2477 mL | 4.4954 mL |
| 10 mM | 0.2248 mL | 1.1238 mL | 2.2477 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet