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Chemical Structure| 317318-84-6 Chemical Structure| 317318-84-6
Chemical Structure| 317318-84-6

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CAS No.: 317318-84-6

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GW0742 is a highly effective PPARβ and PPARδ agonist, exhibiting an IC50 of 1 nM for human PPARδ in binding assays, and EC50 values of 1 nM, 1.1 μM, and 2 μM for human PPARδ, PPARα, and PPARγ, respectively.

Synonyms: GW610742

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Product Details of GW0742

CAS No. :317318-84-6
Formula : C21H17F4NO3S2
M.W : 471.49
SMILES Code : O=C(O)COC1=CC=C(SCC2=C(C)N=C(C3=CC=C(C(F)(F)F)C(F)=C3)S2)C=C1C
Synonyms :
GW610742
MDL No. :MFCD07369423
InChI Key :HWVNEWGKWRGSRK-UHFFFAOYSA-N
Pubchem ID :9934458

Safety of GW0742

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description Reference
human adipose-derived mesenchymal stem cells (ASCs) 12.5 μM 1 day GW0742 almost completely suppressed the antibacterial activity of 1,25(OH)2D3 activated and unactivated ASCs PMC7367313
RAW264.7 cells 10 μM 16 hours To investigate the effects of GW0742 on cytokine secretion in RAW264.7 cells. Results showed that GW0742 significantly reduced palmitic acid-induced secretion of TNF-α and MCP-1. PMC3490079
AML12 cells 10 μM 16 hours To investigate the effects of GW0742 on insulin signaling in AML12 cells. Results showed that GW0742 significantly increased the expression of pAkt/Akt and pIRS-1/IRS-1. PMC3490079
Primary cortical neurons 1 μM 24 hours GW0742 failed to protect primary neurons against glutamate-induced cell death. PMC4310027
Primary microglia 1 μM 24 hours GW0742 did not significantly affect the survival of primary microglia. PMC4310027
HepG2 cells 10 μM 24 hours To investigate the effects of GW0742 on lipid accumulation and inflammatory markers in HepG2 cells. Results showed that GW0742 significantly reduced palmitic acid-induced lipid vacuoles and decreased NF-κB expression. PMC3490079
macrophages 100 nM 24 hours To evaluate the effect of GW0742 on the inflammatory response in macrophages, results showed that GW0742 treatment reduced LPS-induced iNOS and MCP1 mRNA levels. PMC3171871
Neuron-microglia co-cultures 1 μM 48 hours GW0742 significantly increased MAP-2 immunoreactivity in neuron-microglia co-cultures, indicating its ability to prevent inflammation-induced neuronal death. PMC4310027

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description Reference
C57Bl/6 mice Whole-brain irradiation model Dietary administration 100 ppm Started 14 days before irradiation and continued until euthanasia GW0742 prevented the acute increase in IL-1β mRNA and ERK phosphorylation levels after WBI and inhibited the WBI-induced activation of hippocampal microglia in mice. However, GW0742 did not restore hippocampal neurogenesis following WBI, nor did it prevent early delayed hippocampal-dependent cognitive impairment after WBI. PMC3884086
Mice 5XFAD mouse model Oral 30 mg/kg Once daily for 2 weeks GW0742 treatment significantly reduced the Aβ load in the brains of 5XFAD mice and decreased microglial activation, along with a reduction in proinflammatory mediators, ultimately attenuating neuronal loss. PMC4310027
Rats Type 2 diabetic rat model Oral gavage 10 mg/kg/day Once daily for 10 weeks To investigate the effects of GW0742 on fatty liver changes in a type 2 diabetic rat model. Results showed that GW0742 significantly reduced hepatic fatty infiltration and decreased mRNA expressions of TNF-α, MCP-1, and PGC-1α. PMC3490079
Mice PPAR d knock-in mice Oral gavage 10 mg/kg twice daily for 14 days To evaluate the effect of GW0742 on lipid metabolism in mice, results showed that GW0742 treatment increased total cholesterol and HDL-C levels and reduced TG content in LDL particles. PMC3171871

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.12mL

0.42mL

0.21mL

10.60mL

2.12mL

1.06mL

21.21mL

4.24mL

2.12mL

References

[1]Burdick AD, Bility MT, et al. Ligand activation of peroxisome proliferator-activated receptor-beta/delta(PPARbeta/delta) inhibits cell growth of human N/TERT-1 keratinocytes. Cell Signal. 2007 Jun;19(6):1163-71.

[2]Sznaidman ML, Haffner CD, et al. Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)--synthesis and biological activity. Bioorg Med Chem Lett. 2003 May 5;13(9):1517-21.

[3]Nandhikonda P, Yasgar A, Baranowski AM, et al. Peroxisome proliferation-activated receptor δ agonist GW0742 interacts weakly with multiple nuclear receptors, including the vitamin D receptor. Biochemistry. 2013;52(24):4193-203

[4]Sznaidman ML, Haffner CD, Maloney PR, Fivush A, Chao E, Goreham D, Sierra ML, LeGrumelec C, Xu HE, Montana VG, Lambert MH, Willson TM, Oliver WR Jr, Sternbach DD. Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)--synthesis and biological activity. Bioorg Med Chem Lett. 2003 May 5;13(9):1517-21. doi: 10.1016/s0960-894x(03)00207-5. PMID: 12699745.

[5]Burdick AD, Bility MT, Girroir EE, Billin AN, Willson TM, Gonzalez FJ, Peters JM. Ligand activation of peroxisome proliferator-activated receptor-beta/delta(PPARbeta/delta) inhibits cell growth of human N/TERT-1 keratinocytes. Cell Signal. 2007 Jun;19(6):1163-71. doi: 10.1016/j.cellsig.2006.12.007. Epub 2007 Jan 3. PMID: 17254750; PMCID: PMC1913217.

[6]Smith SA, Monteith GR, Robinson JA, Venkata NG, May FJ, Roberts-Thomson SJ. Effect of the peroxisome proliferator-activated receptor beta activator GW0742 in rat cultured cerebellar granule neurons. J Neurosci Res. 2004 Jul 15;77(2):240-9. doi: 10.1002/jnr.20153. PMID: 15211590.

[7]Kuo SC, Ku PM, Chen LJ, Niu HS, Cheng JT. Activation of receptors δ (PPARδ) by agonist (GW0742) may enhance lipid metabolism in heart both in vivo and in vitro. Horm Metab Res. 2013 Nov;45(12):880-6. doi: 10.1055/s-0033-1348317. Epub 2013 Jun 26. PMID: 23803968.

 

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