GW9662

Biological Activity

GW9662 is a selective PPAR antagonist for PPARγ with IC50 of 3.3 nM, with at least 100 to 1000-fold functional selectivity in cells with PPARγ versus PPARα and PPARδ.

Product Citations

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  Acta Pharmacol Sin. 2020 Mar;41(3):373-382.

  Asiatic acid prevents renal fibrosis in UUO rats via promoting the production of 15d-PGJ2, an endogenous ligand of PPAR-γ
  GW9662 purchased from AbMole

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  J Cell Mol Med. 2020 Jun;24(12):6833-6845.

  Seizure-induced impairment in neuronal ketogenesis: Role of zinc-α2-glycoprotein in mitochondria
  GW9662 purchased from AbMole

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  Life Sci. 2019 Dec 1;238:116979.

  Effects of progesterone on glucose uptake in neurons of Alzheimer's disease animals and cell models.
  GW9662 purchased from AbMole

Customer Product Validations & Biological Datas

	Source	J Cell Mol Med (2020 Jun). Figure 2. Pioglitazone (Abmole Bioscience, Houston, TX, USA)
	Method	drug treatments
	Cell Lines	Neurons
	Concentrations	-
	Incubation Time	24 hours
	Results	Compared to the DMSO group, a 24-hour treatment with pioglitazone increased the levels of the ZAG protein (1.013 ± 0.135 vs 0.654 ± 0.090, P = 0.004, n = 4) and AZGP1 mRNA (1.474 ± 0.078 vs 1, P = 0.003, n = 3) (Figure 2B,C), while GW9662 significantly decreased the levels of the ZAG protein (0.361 ± 0.097 vs 0.654 ± 0.090, P = 0.013, n = 4) and AZGP1 mRNA (0.482 ± 0.153 vs 1, P = 0.002, n = 3) (Figure 2B,C).

	Source	Oncol Lett (2018). Figure 5. GW9662
	Method	western blotting
	Cell Lines	EC109 cells
	Concentrations	40 μM
	Incubation Time	72 h
	Results	GW9662 treatment attenuated the inhibitory effects of carotenoids on EC109 cell viability and the increase in PPARγ protein levels induced by carotenoids was reduced with GW9662 pre.treatment in EC109 cells.

Chemical Information

Molecular Weight	276.68
Formula	C13H9ClN2O3
CAS Number	22978-25-2
Solubility (25°C)	DMSO ≥ 40 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Collino M, et al. Kidney Int. The selective PPARgamma antagonist GW9662 reverses the protection of LPS in a model of renal ischemia-reperfusion.

[2] Seargent JM, et al. Br J Pharmacol. 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.

[3] Leesnitzer LM, et al. Biochemistry. Functional consequences of cysteine modification in the ligand binding sites of peroxisome proliferator activated receptors by GW9662.