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Purity: ≥98%
BMS-687453 (BMS687453) is a potent and selective peroxisome proliferator activated receptor (PPAR) alpha agonist with the potential to be used for the treatment of atherosclerosis and dyslipidemia. It exhibits an EC50 and IC50 of 10 nM and 260 nM for human PPARα and 4100 nM and >15000 nM for PPARγ in PPAR-GAL4 transactivation assays. BMS-687453 has an excellent pharmacological and safety profile in preclinical studies and thus was selected as a drug candidate for the treatment of atherosclerosis and dyslipidemia. BMS-687453 (10, 50, 100, p.o.) dose-dependently increases serum ApoA1 protein levels and low-density lipoprotein-cholesterol (LDLc) levels in mice.
| ln Vitro |
With an EC50 and IC50 of 10 nM and 260 nM for human PPARα and approximately 410-fold and more than 57-fold selectivity vs human PPARγ of 4100 nM and >15000 nM in PPAR- GAL4 transactivations, BMS-687453 is a strong and selective PPARα agonist. In HepG2 cells, BMS-687453 shows a ∼50-fold selectivity and high PPARα potency (EC50 = 47 nM) in comparison to PPARγ (EC50 = 2400 nM). BMS-687453 is still a complete PPARα agonist in both species, but it exhibits less potent activities in rodent PPARα functional assays, with a moderate EC50 of 426 nM for mice and 488 nM for hamsters[1].
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| ln Vivo |
Low-density lipoprotein cholesterol (LDLc) and serum ApoA1 protein levels in mice are dose-dependently increased by BMS-687453 (10, 50, 100, po). In hamsters fed a high fat diet, BMS-687453 (1, 3, 10 mg/kg, po) lowers HDLc levels[1]. PDK4 mRNA is induced in the liver by BMS-687453, with an ED50 value of 0.24 mg/kg[2]. Male rats treated with 300 mg/kg po of BMS-687453 experience skeletal myofiber degeneration and necrosis, which is characterized by discoid changes, myofibril lysis, hyalinization, and cellular infiltration. For male rats, BMS-687453 (300 mg/kg, po) causes mild toxicity in both the fast and slow-twitch muscles[3].
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| 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
[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 Phar [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 |
| Molecular Formula |
C₂₂H₂₁CLN₂O₆
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| Molecular Weight |
444.86
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| CAS # |
1000998-59-3
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| SMILES |
ClC(C=C1)=CC=C1C2=NC(COC3=CC=CC(CN(C(OC)=O)CC(O)=O)=C3)=C(C)O2
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.62 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2479 mL | 11.2395 mL | 22.4790 mL | |
| 5 mM | 0.4496 mL | 2.2479 mL | 4.4958 mL | |
| 10 mM | 0.2248 mL | 1.1239 mL | 2.2479 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 BMS-687453 (A and B) and BMS-711939 (C and D) raise HDLc (A and C) and ApoA1 (B and D) in human ApoA1 transgenic mice.
Synergistic increase in fecal cholesterol excretion by the combination of PPARα and LXR agonists in SV/129 wild-type or PPARα-humanized mice (A) and human ApoA1 transgenic mice (B and C).J Pharmacol Exp Ther.2008 Dec;327(3):716-26. |
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 BMS-687453 lowers serum triglycerides (A) and LDLc (B) in fat-fed hamsters.J Pharmacol Exp Ther.2008 Dec;327(3):716-26.
Liver gene induction occurs at a much lower dose in PPARα-humanized mice compared with mice harboring wild-type (mouse) PPARα.J Pharmacol Exp Ther.2008 Dec;327(3):716-26. |
BMS-711939 lowers serum triglycerides (A) and LDLc (B) in fat-fed hamsters.
Plasma triglyceride lowering correlates with hepatic gene induction.J Pharmacol Exp Ther.2008 Dec;327(3):716-26. |
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