GW9662
GW9662 is a potent antagonist of PPARγ with IC50 value of 3.3 nM [1].
PPARγ belongs to the nuclear receptor superfamily, the inhibition of it is a strategy for treatment of several cancers, including breast. GW9662 acts as a potent, irreversible and selective PPARγ antagonist in both cell-free and cell-based assays. It modifies a cysteine residue in the ligand-binding site of PPARγ. In three breast cell lines including MCF7, MDA-MB-231 and MDA-MB-468, GW9662 suppresses the cell viability with IC50 values ranging from 20-30 μM. In addition, GW9662 is reported to abolish the protection of LPS in a model of renal ischemia/reperfusion (I/R). In this model, the renal/glomerular dysfunction, tubular dysfunction and reperfusion injury caused by I/R can be significantly attenuated by LPS, and administration of GW9662 reverses this [2, 3].
References:
[1] Fong WH, Tsai HD, Chen YC, Wu JS, Lin TN. Anti-apoptotic actions of PPAR-gamma against ischemic stroke. Mol Neurobiol. 2010 Jun; 41 (2-3): 180-6.
[2] Seargent JM, Yates EA, Gill JH. GW9662, a potent antagonist of PPARgamma, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPARgamma agonist rosiglitazone, independently of PPARgamma activation. Br J Pharmacol. 2004 Dec; 143 (8): 933-7.
[3] Collino M, Patel NS, Lawrence KM, Collin M, Latchman DS, Yaqoob MM, Thiemermann C. The selective PPARgamma antagonist GW9662 reverses the protection of LPS in a model of renal ischemia-reperfusion. Kidney Int. 2005 Aug; 68 (2): 529-36.
- 1. Ai Wei, Qi Gao, et al. "Inhibition of DNA methylation derepresses PPARγ and attenuates pulmonary fibrosis." Br J Pharmacol. 2021 Aug 11. PMID:34378791
- 2. WeijieSuna, XiaoyuDuana, et al. "Adipogenic activity of 2-ethylhexyl diphenyl phosphate via peroxisome proliferator-activated receptor γ pathway." Science of The Total Environment. Available online 18 November 2019, 134810.
- 3. LianyingZhangab, WeijieSuna, et al. "Promoting differentiation and lipid metabolism are the primary effects for DINP exposure on 3T3-L1 preadipocytes." Environmental Pollution. Available online 13 September 2019, 113154.
- 4. Guo X, Yan F, et al. "SIRT3 inhibits Ang II-induced transdifferentiation of cardiac fibroblasts through β-catenin/PPAR-γ signaling." Life Sci. 2017 Oct 1;186:111-117. PMID:28760678
| Storage | Store at -20°C |
| M.Wt | 276.68 |
| Cas No. | 22978-25-2 |
| Formula | C13H9ClN2O3 |
| Solubility | insoluble in H2O; ≥13.75 mg/mL in DMSO; ≥9.08 mg/mL in EtOH with ultrasonic |
| Chemical Name | 2-chloro-5-nitro-N-phenylbenzamide |
| SDF | Download SDF |
| Canonical SMILES | C1=CC=C(C=C1)NC(=O)C2=C(C=CC(=C2)[N+](=O)[O-])Cl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
Human breast cancer cell lines MCF7, MDA-MB-468 and MDA-MB-231 |
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Preparation method |
The solubility of this compound in DMSO is >13.75 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. |
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Reacting condition |
0.1 ~ 50 μM; 72 hrs |
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Applications |
In all the three human breast cancer cell lines, GW9662 resulted in comparable loss of cell viability. In MDA-MB-231 cells, GW9662 in combination with Rosiglitazone caused an additive effect on cell survival instead of the predicted subtractive effect. Analysis of the cellular growth kinetics of MDA-MB-231 cells further confirmed that GW9662 did not prevent Rosiglitazone-induced growth inhibition, but strengthened the effect of Rosiglitazone. |
| Animal experiment [2]: | |
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Animal models |
A rat model of renal ischemia-reperfusion (I/R) |
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Dosage form |
1 mg/kg; i.p.; 12 and 24 hrs prior to ischemia |
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Applications |
In a rat model of renal I/R, GW9662 abolished lipopolysaccharide (LPS) pretreatment-induced creatinine clearance. Administration of GW9662 to LPS-pretreated I/R rats increased fractional excretion of Na+ and reduced urine flow, thus attenuating the protective effect on tubular dysfunction mediated by LPS. In addition, the attenuation in serum aspartate aminotransferase and γ-glutamyl transferase after LPS pretreatment was reversed by GW9662. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Seargent JM, Yates EA, Gill JH. GW9662, a potent antagonist of PPARgamma, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPARgamma agonist rosiglitazone, independently of PPARgamma activation. Br J Pharmacol. 2004 Dec; 143 (8): 933-7. [2] Collino M, Patel NS, Lawrence KM, Collin M, Latchman DS, Yaqoob MM, Thiemermann C. The selective PPARgamma antagonist GW9662 reverses the protection of LPS in a model of renal ischemia-reperfusion. Kidney Int. 2005 Aug; 68 (2): 529-36. |
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| Description | GW9662 is a selective, irreversible and effective antagonist of PPARγ with IC50 value of 3.3 µM for human PPARγ. | |||||
| Targets | PPARγ | |||||
| IC50 | 3.3 µM (human) | |||||
Quality Control & MSDS
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