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Purity: ≥98%
GW 6471 (GW6471; GW-6471) is a novel and potent PPARα antagonist with an IC50 of 0.24 μ M. GW6471 can enhance the binding affinity of the PPAR α ligand-binding domain to the co-repressor proteins SMRT and NCoR.
| ln Vitro |
GW6471 significantly reduced GW409544-induced PPARα activation in a cell-based gene reporter test, with an IC50 of 0.24 μM [1]. Using the MTT assay, the functional impact of PPARα on the viability of renal cell carcinoma (RCC) cells was evaluated. For a duration of 72 hours, Caki-1 (VHL wild-type) and 786-O (VHL mutant) cells were sterilely treated with either the specific PPARα-selective antagonist GW6471 or the specific PPARα agonist WY14,643 at doses ranging from 12.5 to 100 μM. The vitality of the cells was then evaluated. WY14,643 did not affect cell viability or cause a gradual increase in it, but GW6471 dramatically reduced cell viability in both cell lines in a foot-dependent manner, up to almost 80% [2].
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| ln Vivo |
In vivo anti-activity of PPARα antagonist was evaluated using a tumor subcutaneous xenograft model. Nude mice (Nu/Nu) were given subcutaneous injections of Caki-1 cells. The medication GW6471 was given intraperitoneally every day for four weeks at a dose of 20 mg/kg mouse body weight, which was found to be effective in an in vivo dose-response study and validated here, once the tumor mass had grown to a diameter of approximately 5 mm. The tumor growth of the animals treated with GW6471 and those treated with vehicle differed significantly. The animals' body weight indicated that there was no toxicity at the GW6471 dosage, and laboratory results, such as liver and renal function tests, showed no negative effects. c-Myc levels in tumors were assessed to illustrate GW6471's inhibitory effect, and results indicated a significant decrease in tumors in animals treated with GW6471 [3].
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| References |
[1]. Xu HE, et al. Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha. Nature. 2002 Feb 14;415(6873):813-7.
[2]. Abu Aboud O, et al. Inhibition of PPARα induces cell cycle arrest and apoptosis, and synergizes with glycolysisinhibition in kidney cancer cells. PLoS One. 2013 Aug 7;8(8):e71115. [3]. Abu Aboud O, et al. PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth. Am J Physiol Cell Physiol. 2015 Jun 1;308(11):C890-8 |
| Molecular Formula |
C35H36F3N3O4
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|---|---|
| Molecular Weight |
619.6733
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| CAS # |
880635-03-0
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| SMILES |
CCC(NC[C@@H](N/C(C)=C\C(C1=CC=C(C(F)(F)F)C=C1)=O)CC2=CC=C(OCCC3=C(C)OC(C4=CC=CC=C4)=N3)C=C2)=O
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| InChi Key |
TYEFSRMOUXWTDN-DYQICHDWSA-N
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| InChi Code |
InChI=1S/C35H36F3N3O4/c1-4-33(43)39-22-29(40-23(2)20-32(42)26-12-14-28(15-13-26)35(36,37)38)21-25-10-16-30(17-11-25)44-19-18-31-24(3)45-34(41-31)27-8-6-5-7-9-27/h5-17,20,29,40H,4,18-19,21-22H2,1-3H3,(H,39,43)/b23-20-/t29-/m0/s1
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| Chemical Name |
(S,Z)-N-(3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)-2-((4-oxo-4-(4-(trifluoromethyl)phenyl)but-2-en-2-yl)amino)propyl)propionamide
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| Synonyms |
GW6471; GW-6471; GW 6471
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
DMSO : ~83.33 mg/mL (~134.47 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.36 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 20.8 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: 2.08 mg/mL (3.36 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 20.8 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: ≥ 2.08 mg/mL (3.36 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 | 1.6138 mL | 8.0688 mL | 16.1376 mL | |
| 5 mM | 0.3228 mL | 1.6138 mL | 3.2275 mL | |
| 10 mM | 0.1614 mL | 0.8069 mL | 1.6138 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.
Products are for research use only; We do not sell to patients
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