GW9662 Chemical Properties

Melting point:

158-159 °C (lit.)

Boiling point:

360.9±32.0 °C(Predicted)

Density 

1.440±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: 26 mg/mL, soluble

form 

solid

pka

11.77±0.70(Predicted)

color 

white

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.

InChIKey

DNTSIBUQMRRYIU-UHFFFAOYSA-N

CAS DataBase Reference

22978-25-2(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36-43

Safety Statements 

26-36/37-24/25-22

WGK Germany 

3

HS Code 

29242990

MSDS

• Language:English Provider:SigmaAldrich

GW9662 Usage And Synthesis

Description

GW-9662 (22978-25-2) is a selective PPARγ antagonist (IC50 = 3.3, 32 and 2000 nM for PPARγ, PPARα and PPARδ respectively).1 Blocks the inhibition of osteoclast formation induced by IL-4 (1-2 μM).2 Displays anticancer activity inhibits growth of human mammary tumor cell lines.3 GW-9662 is a useful tool for dissecting the involvement of PPARγ in cellular physiology.4,5

Chemical Properties

Off-White Solid

Uses

An irreversible PPAR antagonist

Uses

GW9662 has been used as a peroxisome proliferator activated receptor γ (PPARγ) antagonist in human pluripotent stem cells, in phenylephrine stimulated cardiomyocytes and to inhibit the protective effect of telmisartan pheochromocytoma, PC12 cells.

Uses

A cell-permeable, selective and irreversible PPAR antagonist (IC50 = 3.3 nM, 32 nM, and 2 for PPAR, PPARa, and PPARd, respectively). Reported to covalently modify a cysteine residue in the binding site of PPAR. At a concentration of 10 , also

Definition

ChEBI: GW 9662 is a member of benzamides.

Biological Activity

Selective PPAR γ antagonist (IC 50 values are 3.3, 32 and 2000 nM for PPAR γ , PPAR α and PPAR δ respectively). Blocks the inhibition of osteoclast formation induced by IL-4 in the low micromolar range (1-2 μ M), therefore is more potent than BADGE (2,2-Bis[4-(2,3-epoxypropoxy)phenyl]propane ). Anticancer, inhibits growth of human mammary tumor cell lines.

Biochem/physiol Actions

GW9662 (2-chloro-5-nitrobenzanilide) binds to the ligand binding site of the peroxisome proliferator activated receptor γ (PPARγ) and results in the inhibition of adipocyte differentiation. It favors cell growth suppression in breast cancer cell lines even in the presence of PPARγ agonist rosiglitazone. It stimulates M2c macrophages differentiation and triggers growth arrest-specific 6 (Gas6) expression. GW9662 co treatment with other PPARγ ligands elicits antiproliferative effects on the glioblastoma stem cells and could be a potent therapeutic agent.

Synthesis

To a stirred solution of 2-chloro-5-nitrobenzoyl chloride (5.03 g, 22.9 mmol) and triethylamine (3.51 mL, 25.1 mmol) in dichloromethane (CH2Cl2) maintained at 0°C in a nitrogen atmosphere was slowly added aniline (2.19 mL, 24.0 mmol) dropwise. The reaction mixture was continued to be stirred at 0 °C for 5 min, then brought to room temperature and stirred for 15 min. Upon completion of the reaction, the solution was diluted with ethyl acetate (EtOAc, 300 mL) and washed sequentially with 1.0 M HCl, water, 1.0 M NaHCO3 and saturated saline (100 mL each). The organic phase was dried over anhydrous magnesium sulfate (MgSO4) and concentrated by rotary evaporation to give a light yellow solid (5.32 g). The solid was purified by recrystallization from ethyl acetate to give a white solid 2-chloro-5-nitro-N-phenylbenzamide (3.34 g, 53% yield) with a melting point of 155-156 °C. The product was confirmed by 1H NMR (CDCl3, 400 MHz): δ 8.63 (d, 1H, J=2.7 Hz), 8.28 (dd, 1H, J=2.7, 8.9 Hz), 7.81 (br s, 1H), 7.68-7.63 (m, 3H), 7.42 (t, 2H, J=7.9 Hz), 7.23 (t, 1H, J= 7.5 Hz). The mass spectrum (ES-) showed m/z 275.1 ([M-H]-). Elemental analysis (C13H9ClN2O3) calculated values: C, 56.43; H, 3.28; N, 10.13; measured values: C, 56.33; H, 3.30; N, 10.03.

storage

Store at RT

References

[1] LISA M. LEESNITZER. Functional Consequences of Cysteine Modification in the Ligand Binding Sites of Peroxisome Proliferator Activated Receptors by GW9662[J]. Biochemistry Biochemistry, 2002, 41 21: 6640-6650. DOI:10.1021/bi0159581
[2] A C BENDIXEN. IL-4 inhibits osteoclast formation through a direct action on osteoclast precursors via peroxisome proliferator-activated receptor gamma 1.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2001, 98 1: 2443-2448. DOI:10.1073/pnas.041493198
[3] JILL M SEARGENT J H G Elisabeth A Yates. 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.[J]. British Journal of Pharmacology, 2004, 143 8: 933-937. DOI:10.1038/sj.bjp.0705973
[4] YUJIE CHENG  Sha L  Zhi Dong. β-Caryophyllene ameliorates the Alzheimer-like phenotype in APP/PS1 Mice through CB2 receptor activation and the PPARγ pathway.[J]. Pharmacology, 2014, 94 1-2: 1-12. DOI:10.1159/000362689
[5] ZUN-JING LIU. Curcumin protects neurons against oxygen-glucose deprivation/reoxygenation-induced injury through activation of peroxisome proliferator-activated receptor-γ function[J]. Journal of Neuroscience Research, 2014, 92 11: 1549-1559. DOI:10.1002/jnr.23438

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