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BMS 687453

Catalog No.GC15995

PPARα agonist

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BMS 687453 Chemical Structure

Cas No.: 1000998-59-3

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5mg
$85.00
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10mg
$139.00
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25mg
$324.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

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.
[2]. Mukherjee R, et al. Novel peroxisome proliferator-activated receptor alpha agonists lower low-density lipoprotein and triglycerides, raise high-density lipoprotein, and synergistically increase cholesterol excretion with a liver X receptor agonist. J Pharmacol Exp Ther. 2008 Dec;327(3):716-26.
[3]. Vassallo JD, et al. Biomarkers of drug-induced skeletal muscle injury in the rat: troponin I and myoglobin. Toxicol Sci. 2009 Oct;111(2):402-12.

Background

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.

Chemical Properties

Cas No. 1000998-59-3 SDF
Chemical Name 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
Formula C22H21ClN2O6 M.Wt 444.9
Solubility DMSO: 30 mg/ml Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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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
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Average Rating: 5 ★★★★★ (Based on Reviews and 27 reference(s) in Google Scholar.)

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