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Purity: ≥98%
| Targets |
BMS-711939 targets the peroxisome proliferator-activated receptor alpha (PPARα), a nuclear receptor that regulates lipid metabolism, inflammation, and energy homeostasis. Activation of PPARα leads to increased fatty acid oxidation, reduced triglyceride levels, and improved insulin sensitivity. BMS-711939 is a potent and specific PPARα agonist with an EC50 of 4 nM for human PPARα and >1000-fold selectivity over PPARγ.
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| ln Vitro |
BMS-711939, an analog of BMS-687453, it is a new powerful and selective PPAR alpha agonist. In PPAR-GAL4 transactivation assays, it has an EC50 and IC50 of 4 nM for human PPARα and >1000-fold selectivity compared to human PPARγ (EC50 of 4.5 μM) and PPARδ (EC50 > 100 μM). BMS-711939 was chosen as a medication candidate for the treatment of dyslipidemia and atherosclerosis due to its strong pharmacological and safety profile in preclinical studies. Low-density lipoprotein-cholesterol (LDLc) and serum ApoA1 protein levels in mice are dose-dependently increased by BMS-711939 (10, 50, 100, p.o.).
In vitro, BMS-711939 demonstrates potent and specific PPARα agonism with an EC50 of 4 nM for human PPARα. It shows >1000-fold selectivity over PPARγ (EC50 of 4.5 μM) and >1000-fold over other receptors in PPAR-GAL4 transactivation assays. The compound's high potency and selectivity make it a valuable tool for studying PPARα-mediated signaling pathways and metabolic regulation. |
| ln Vivo |
BMS-711939 was chosen as a medication candidate for the treatment of dyslipidemia and atherosclerosis due to its strong pharmacological and safety profile in preclinical studies. Low-density lipoprotein-cholesterol (LDLc) and serum ApoA1 protein levels in mice are dose-dependently increased by BMS-711939 (10, 50, 100, p.o.). The volume of distribution ranged from 0.7 L/kg (rat) to 3.5 L/kg (cynomolgus monkey), which is comparable to the total body water in the rat and greater than the total body water in the mouse, rat, and monkey. BMS-687453 exhibits low plasma clearance in the mouse, rat, and monkey and moderate plasma clearance in the dog.
In vivo, BMS-711939 has demonstrated excellent efficacy and safety in preclinical studies. As a potent and specific PPARα agonist, it is expected to have beneficial effects on lipid metabolism and insulin sensitivity. The compound has shown excellent efficacy and safety in vivo in preclinical studies. Specific animal model data are not detailed in the available sources beyond its characterization as a PPARα agonist. |
| Enzyme Assay |
In PPAR-GAL4 transactivation assays, BMS-711939, an analogue of BMS-687453, exhibits >1000-fold selectivity compared to human PPARγ (EC50 of 4.5 μM) and PPARδ (EC50 > 100 μM). It is a novel potent and selective peroxisome proliferator activated receptor (PPAR) alpha agonist. In PPAR-GAL4 transactivation assays, BMS-687453 is a strong and selective PPARα agonist, with EC50 and IC50 values of 10 nM and 260 nM for human PPARα and 4100 nM and >15000 nM for PPARγ. The primary screen for figuring out a compound's PPARα and PPARγ binding affinity is a homogeneous, fluorescent polarization PPARα and PPARγ binding assay. The GAL4-LBD assays are used to measure the functional activity of PPARα and PPARγ agonists in humans. The chimeric GAL4/PPARα assay format is used to test the functional activities of PPARα in vitro in hamsters, rats, and mice. With all parameters floating and an XLfit 4 parameter fit, the data are reported as an EC50value. To test the leading compounds further, full length human PPARα and PPARγ co-transfection assays in HepG2 cells are utilized (BMS-687453).
The PPARα transactivation assay for BMS-711939 involves using a GAL4-PPARα fusion protein and a luciferase reporter gene containing GAL4 response elements. HEK293 cells are transfected with the GAL4-PPARα expression plasmid and the reporter plasmid. Cells are treated with varying concentrations of BMS-711939 for 24 hours, and luciferase activity is measured using a luminometer. EC50 values are calculated from dose-response curves. Selectivity is assessed by testing against PPARγ and other nuclear receptors using similar assays. |
| Cell Assay |
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 strong activity in rodent PPARα functional tests, with a moderate EC50 of 426 nM for mice and 488 nM for hamsters.
To evaluate the cellular activity of BMS-711939, hepatocytes or other PPARα-expressing cell lines are seeded in 96-well plates and treated with varying concentrations of BMS-711939. PPARα target gene expression (such as CPT1A, ACOX1) is measured by quantitative RT-PCR. Alternatively, the compound's effect on lipid accumulation can be assessed using Oil Red O staining or triglyceride quantification. The EC50 for induction of target gene expression or reduction of lipid accumulation is calculated. |
| Animal Protocol |
Formulated in 2% Tween 80 and 0.5% CMC (carboxymethylcellulose) in 97.5% Gibco distilled water; 5 mL/kg; Oral gavage. Male 6 8 week old human apoA1 transgenic mice
The in vivo efficacy of BMS-711939 is evaluated in animal models of dyslipidemia or non-alcoholic fatty liver disease (NAFLD). Rodents are fed a high-fat diet to induce metabolic dysfunction and then treated with BMS-711939 orally at various doses. Plasma lipid levels (triglycerides, cholesterol, free fatty acids) are measured. Hepatic triglyceride content is determined by biochemical assay. Liver histology is performed to assess steatosis. The compound's effects on insulin sensitivity can be assessed by glucose tolerance tests. |
| ADME/Pharmacokinetics |
BMS-711939 is characterized as being orally bioavailable with demonstrated efficacy in preclinical studies. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 499.48 and a molecular formula of C26H24F3N3O4. It is a small molecule with properties suitable for oral administration.
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| Toxicity/Toxicokinetics |
BMS-711939 has demonstrated excellent safety in preclinical studies. Specific toxicity data are not detailed in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is a potent and specific PPARα agonist, and its safety profile would be expected to be consistent with other PPARα agonists. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
BMS-711939 is also known as BMS711939. It is a potent and specific PPARα agonist with an EC50 of 4 nM for human PPARα and >1000-fold selectivity over PPARγ (EC50 of 4.5 μM). It has demonstrated excellent efficacy and safety in preclinical studies. The compound is used in research related to metabolic disorders, including dyslipidemia and NAFLD.
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| Molecular Formula |
C22H20CLFN2O6
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| Molecular Weight |
462.86
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| Exact Mass |
462.099
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| Elemental Analysis |
C, 57.09; H, 4.36; Cl, 7.66; F, 4.10; N, 6.05; O, 20.74
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| CAS # |
1000998-62-8
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| Related CAS # |
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| PubChem CID |
16727109
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| Appearance |
Solid powder
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| LogP |
4.674
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
636
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC(=CC=1)C1=NC(=C(C)O1)COC1=CC=C(C(=C1)CN(C(=O)OC)CC(=O)O)F
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| InChi Key |
OPHWZEQODBXRCZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H20ClFN2O6/c1-13-19(25-21(32-13)14-3-5-16(23)6-4-14)12-31-17-7-8-18(24)15(9-17)10-26(11-20(27)28)22(29)30-2/h3-9H,10-12H2,1-2H3,(H,27,28)
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| Chemical Name |
2-[[5-[[2-(4-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]methoxy]-2-fluorophenyl]methyl-methoxycarbonylamino]acetic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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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) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1605 mL | 10.8024 mL | 21.6048 mL | |
| 5 mM | 0.4321 mL | 2.1605 mL | 4.3210 mL | |
| 10 mM | 0.2160 mL | 1.0802 mL | 2.1605 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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