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Purity: ≥98%
GW9662 (GW-9662; GW 9662) is an irreversible and selective inhibitor of PPAR (peroxisome proliferator-activated receptor) with potential anticancer activity. It inhibits PPARγ with an IC50 of 3.3 nM in a cell-free assay, and shows >100-fold selectivity for PPARγ over PPARα and PPARδ. GW9662 prevented activation of PPARgamma and inhibited growth of human mammary tumour cell lines. GW9662 may permit use of anti-ER strategies to inhibit breast cancer in ER- patients. GW9662 suppresses the cell viability with IC50 values ranging from 20-30μM.
| Targets |
PPARγ: (IC50 = 3.3 nM)
PPARα: (IC50 = 32 nM) PPARδ: (IC50 = 2000 nM) |
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| ln Vitro |
GW9662 has the ability to suppress radioligand binding to PPARγ, PPARα, and PPARδ, with corresponding pIC50 values of 8.48±0.27 (IC50=3.3 nM; n = 10), 7.49±0.17 (IC50=32 nM; n = 9), and 5.69±0.17 (IC50=2000 nM; n = 3). The binding studies with PPARα and PPARδ show that GW9662 is 10- and 600-fold less effective, respectively, with a nanomolar IC50 against PPARγ. GW9662 effectively and selectively blocks full-length PPARγ in cell-based reporter assays[1]. When paired with either 50 μM BRL 49653 (P=0.001) or 10 μM GW9662 (P=0.01) alone, co-treatment with both 50 μM BRL 49653 and 10 μM GW9662 leaves a significantly less number of viable cells after 7 days[2].
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| ln Vivo |
Both BADGE- and GW9662(1 mg/kg, ip)-treated mice had significantly greater bone marrow (BM) nucleated cell counts than the aplastic anemia (AA) group[3]. In rats, GW9662 (1 mg/kg, ip) significantly reduces the renoprotective benefits of lipopolysaccharide (LPS)[4].
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| Enzyme Assay |
Binding Assays. [1]
SPAs for all three PPARs were performed as previously described for PPARγ. In brief, the human PPARα, PPARγ, and PPARδ ligand binding domains (LBDs) were expressed in E. coli as polyhistidine-tagged fusion proteins. Receptors were immobilized on SPA beads (Amersham Pharmacia) by addition of the desired receptor (15 nM) to a slurry of streptavidin-modifed SPA beads (0.5 mg/mL) in assay buffer. The mixture was allowed to equilibrate for at least 1 h at room temperature, and the beads were pelleted by centrifugation at 1000g. The supernate was discarded, and the beads were resuspended in the original volume of fresh assay buffer with gentle mixing. The centrifugation/resuspension procedure was repeated, and the resulting slurry of receptor-coated beads was used immediately or stored at 4 °C for up to 1 week before use. [3H]GW2331, [3H]rosiglitazone, and [3H]GW2443 were used as radioligands for determination of competition binding to PPARα, PPARγ, and PPARδ, respectively. Unless otherwise indicated, the buffer used for all assays was 50 mM HEPES (pH 7), 50 mM NaCl, 5 mM CHAPS, 0.1 mg/mL BSA, and 10 mM DTT. For some experiments, the HEPES (pH 7) was replaced with 50 mM Tris (pH 8). Preparation of GW9662-Modified PPARγ for Mass Spectral Analysis. [1] A stock solution of GW9662 in dimethyl sulfoxide was added to a 20 μM solution of PPARγ in 50 mM Tris (pH 8), 50 mM NaCl, 5 mM CHAPS, 0.1 mg/mL BSA, and 10 mM DTT. The final concentration of GW9662 was 40 μM. The solution was incubated at 4 °C followed by mass spectral analysis as described below. |
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| Cell Assay |
Cell-Based Reporter Assays.[1]
The ability of GW9662 to activate PPAR-mediated reporter gene transcription was assessed using GAL4 chimeras of the human receptors and a (UAS)5-tk-SPAP reporter plasmid as previously described for PPARγ, PPARα, and PPARδ. GW9662 antagonism of ligand-induced gene transcription was measured as previously described. Antagonism of agonist-induced reporter gene transcription was done by titrating varying concentrations of GW9662 in the presence of a constant concentration of activating ligand. The activating ligands used were 100 nM rosiglitazone for PPARγ, 8 nM GW7647 for PPARα, and 0.55 μM GW2433 for PPARδ, respectively. The effects of GW9662 on activation of PPARγ, PPARα, and PPARδ were also assessed using full-length human receptors and a reporter construct, (L-FABP)4-tk-Dual-LUC, containing four copies of the L-FABP PPRE upstream of the minimal herpesvirus thymidine kinase promoter and a luciferase reporter gene. The receptor plasmids contained the appropriate full-length PPAR cDNA plus 9 base pairs of Kozak consensus sequence cloned into the TOPO site of pcDNA3.1-TOPO. Briefly, HEK293 cells were cultured in Minimum Essential Media containing 10% fetal calf serum, 1% penicillin/streptomycin, and 1% fungizone in a humidified incubator (5% CO2 in air) at 37 °C. The cells were seeded at 2 × 104 cells per well in 96 well culture plates the day prior to assay execution. Transfection was accomplished using PolyFect according to the manufacturers' instructions. Transfection mixtures for each well contained 0.167 μg of PPAR plasmid, 0.167 μg of LFABP reporter, and 0.167 μg of a renilla luciferase plasmid as transfection control. Cells were incubated with the transfection mixture for 5 h before treatment with either compound or vehicle for 48 h. Culture plates were assayed using the Dual Luciferase assay system according to the manufacturers' instructions. |
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| Animal Protocol |
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| References |
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| Additional Infomation |
GW 9662 is a member of benzamides.
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| Molecular Formula |
C13H9CLN2O3
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|---|---|
| Molecular Weight |
276.68
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| Exact Mass |
276.03
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| Elemental Analysis |
C, 56.43; H, 3.28; Cl, 12.81; N, 10.13; O, 17.35
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| CAS # |
22978-25-2
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| Related CAS # |
GW9662-d5;2117730-84-2
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| PubChem CID |
644213
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
360.9±32.0 °C at 760 mmHg
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| Melting Point |
171-175 °C(lit.)
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| Flash Point |
172.0±25.1 °C
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| Vapour Pressure |
0.0±0.8 mmHg at 25°C
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| Index of Refraction |
1.676
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| LogP |
2.76
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
19
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| Complexity |
339
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
DNTSIBUQMRRYIU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H9ClN2O3/c14-12-7-6-10(16(18)19)8-11(12)13(17)15-9-4-2-1-3-5-9/h1-8H,(H,15,17)
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| Chemical Name |
2-Chloro-5-nitro- N -phenylbenzamide
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| Synonyms |
GW-9662; GW 9662; GW9662;
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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 |
| 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 (9.04 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 (9.04 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: ≥ 0.5 mg/mL (1.81 mM) (saturation unknown) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 1% DMSO+30% polyethylene glycol+1% Tween 80: 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6143 mL | 18.0714 mL | 36.1428 mL | |
| 5 mM | 0.7229 mL | 3.6143 mL | 7.2286 mL | |
| 10 mM | 0.3614 mL | 1.8071 mL | 3.6143 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.
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Effect of GW9662 on urine flow subsequent to I/R in rats pretreated with lipopolysaccharide.Kidney Int.2005 Aug;68(2):529-36. |
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