Cell lines

Human breast cancer cell lines MCF7, MDA-MB-468 and MDA-MB-231

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 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

0.1 ~ 50 μM; 72 hrs

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 models

A rat model of renal ischemia-reperfusion (I/R)

Dosage form

1 mg/kg; i.p.; 12 and 24 hrs prior to ischemia

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.

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.

GW9662 is a potent antagonist of PPARγ with IC50 value of 3.3nM [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 20-30μM. 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.