GSK0660

Names

[ Name ]:
GSK0660

[Synonym ]:
Methyl 3-[(4-anilino-2-methoxyphenyl)sulfamoyl]-2-thiophenecarboxylate
2-Thiophenecarboxylic acid, 3-[[[2-methoxy-4-(phenylamino)phenyl]amino]sulfonyl]-, methyl ester
gsk0660
Methyl 3-[(4-anilino-2-methoxyphenyl)sulfamoyl]thiophene-2-carboxylate
qcr-147
GSK-0660

Biological Activity

[Description]:

GSK0660 is a potent antagonist of PPARβ and PPARδ, with IC50s of 155 nM for both isoforms.

[Related Catalog]:

Research Areas >> Metabolic Disease

[Target]

PPARβ/δ:155 nM (IC50)

[In Vitro]

GSK0660 is a potent antagonist of PPARβ and PPARδ, with IC50s of both 155 nM, and is nearly inactive on PPARα and PPARγ with IC50s of both >10 μM. GSK0660 antagonizes 100% of the activity of PPARβ/δ with a pIC50 of 6.8. GSK0660 (100 nM) reduces CPT1a (a PPARβ/δ target gene) expression below the basal vehicle-treated level by approximately 50%, but shows no effect on PDK4 expression, which is also a PPARβ/δ target gene in skeletal muscle cells[1]. GSK0660 (0.5 μM) reduces the levels of AMPK and eNOS phosphorylation, and BMP-2, Runx-2 mRNA expression in MC3T3-E1 cells. GSK0660 (0.1 and 0.5 μM) reverses the bezafibrate-induced enchancement of ALP activity on d 7 in MC3T3-E1 cells[2]. GSK0660 (1 μM) markedly blocks GW501516-mediated attenuation of glutamate release, and the effect of GW501516 on ROS generation in BV-2 cells stimulated with LPS. Furthermore, GSK0660 significantly reduces inhibitory effect of GW501516 on the LPS-induced expression of gp91phox mRNA in BV-2 cells[3].

[Cell Assay]

Cell viability is determined by the MTT dye. MC3T3-E1 cells are incubated with bezafibrate (1−1000 μM) for 24, 48, or 72 h, and are pretreated with the AMPK inhibitor compound C (5 μM), PPARβ inhibitor GSK0660 (0.5 μM), PPARα inhibitor MK886 (10 μM), or NOS inhibitor L-NAME (1000 μM) followed by bezafibrate (100 μM) incubation for 48 h. After the incubations, 10 μL of MTT is added to each well of a 96-well microplate, and the microplates are placed in an incubator at 37°C for 4 h. One hundred fifty microliters of DMSO is added to all wells and mixed thoroughly to lyse the cells and dissolve the dark blue crystals. After 10 min, the absorbance is measured at 570 nm using a microplate reader[2].

[References]

[1]. Shearer BG, et al. Identification and characterization of a selective peroxisome proliferator-activated receptor beta/delta (NR1C2) antagonist. Mol Endocrinol. 2008 Feb;22(2):523-9. Epub 2007 Nov 1.

[2]. Zhong X, et al. Bezafibrate enhances proliferation and differentiation of osteoblastic MC3T3-E1 cells via AMPK and eNOS activation. Acta Pharmacol Sin. 2011 May;32(5):591-600.

[3]. Lee WJ, et al. Activation of PPARδ attenuates neurotoxicity by inhibiting lipopolysaccharide-triggered glutamate release in BV-2 microglial cells. J Cell Biochem. 2018 Feb 1.

[Related Small Molecules]

GW9662 | Retinoic acid | Elafibranor | GW501516 | Troglitazone | T0070907 | Pemafibrate | CDDO-Im | Wy-14643 | GW0742 | GW1929 | FH535 | Icariin | Daidzein | Fisetin

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
608.1±65.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₉H₁₈N₂O₅S₂

[ Molecular Weight ]:
418.487

[ Flash Point ]:
321.5±34.3 °C

[ Exact Mass ]:
418.065704

[ PSA ]:
130.35000

[ LogP ]:
2.75

[ Vapour Pressure ]:
0.0±1.7 mmHg at 25°C

[ Index of Refraction ]:
1.650

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

Articles

Foam cell-derived 4-hydroxynonenal induces endothelial cell senescence in a TXNIP-dependent manner.

J. Cell. Mol. Med. 19 , 1887-99, (2015)

Vascular endothelial cell (VEC) senescence is considered an early event in the development of atherosclerotic lesions. Stressful stimuli, in particular oxidative stress, have been linked to premature ...

Activation of PPAR-δ induces microRNA-100 and decreases the uptake of very low-density lipoprotein in endothelial cells.

Br. J. Pharmacol. 172(15) , 3728-36, (2015)

Increased level of very low-density lipoprotein (VLDL) is a key feature of the metabolic syndrome and is associated with cardiovascular diseases. PPAR-δ agonists play a protective role in lipid metabo...

The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.

PLoS Pathog. 10(6) , e1004167, (2014)

Phagocytosis and inflammation within the lungs is crucial for host defense during bacterial pneumonia. Triggering receptor expressed on myeloid cells (TREM)-2 was proposed to negatively regulate TLR-m...