COH-SR4 (Mitochondria uncoupler SR4)

Research use only, not for human use.

SR4 is a uncoupler of mitochondrial oxidative phosphorylation. SR4 modulating amp-dependent kinase (ampk)-mammalian target of rapamycin (mtor) signaling, and inhibiting proliferation of hepg2 hepatocarcinoma cellsSR4 is a novel mitochondrial uncoupler with anti-obesity and anti-diabetic properties.?

SR4 is a uncoupler of mitochondrial oxidative phosphorylation. SR4 modulating amp-dependent kinase (ampk)-mammalian target of rapamycin (mtor) signaling, and inhibiting proliferation of hepg2 hepatocarcinoma cellsSR4 is a novel mitochondrial uncoupler with anti-obesity and anti-diabetic properties.?SR4 increased oxygen consumption, dissipated mitochondrial membrane potential, induced mitochondrial swelling, and decreased intracellular ATP in cultured cells and isolated liver mitochondria.?Oral feeding of SR4 significantly reduced body weight gain, improved glycemic control and insulin resistance, and prevented dyslipidemia in both high-fat-diet (HFD) induced obese and diabetic db/db mice.?SR4 treatment also decreased liver triglycerides and prevented hepatic steatosis in both animal models.?Mitochondrial uncoupling of SR4 results to activation of AMP-activated protein kinase (AMPK), leading to the phosphorylation and inhibition of acetyl-CoA carboxylase (ACC).?Gene analyses by RT-PCR showed SR4 significantly suppressed the mRNA expression of several lipogenic genes and gluconeogenic genes in the liver of HFD obese mice.?RNA sequencing analysis showed that 642 genes were differentially expressed in liver of db/db mice after SR4 treatment (217 upregulated, 425 down-regulated).?Gene ontology analysis by DAVID indicated SR4 upregulated amino acid metabolism and down-regulated lipid and fatty acid synthesis and glucose metabolism.?These studies demonstrate that SR4 may be a promising compound for treatment of T2DM and obesity.

COH-SR4 (1-5 μM; 24 hours) results in a dose-dependent increase in the phosphorylation of AMPK and its substrate ACC in 3T3-L1 preadipocytes, as well as in cancer cells such as HL-60, HeLa, MCF-7.COH-SR4 (3-5 μM; 7 days) significantly inhibits 3T3-L1 adipocyte differentiation in a dose-dependent manner.COH-SR4 (1-5 μM; 24 hours) promotes cell G1 cycle arrest.COH-SR4 significantly reduces intracellular lipid accumulation and downregulates the expression of key adipogenesis-related transcription factors and lipogenic proteins. Western Blot Analysis Cell Line:3T3-L1 preadipocytes, HL-60 cells, HeLa cells, MCF-7 cells Concentration:1 μM, 3 μM, 5 μM Incubation Time:24 hours Result:Indirectly activated AMPK.Cell Cycle Analysis Cell Line:3T3-L1 cells Concentration:1 μM, 3 μM, 5 μM Incubation Time:24 hours Result:Modulated the level of proteins active during S and G2 phases of the cell cycle.

COH-SR4 (5 mg/kg; i.g.; 3x/week; for 6 weeks) reduces body weight and fat mass inhigh fat diet (HFD) obese mice without affecting food intake.COH-SR4 improves glycemic control and dyslipidemia in HFD obese mice.COH-SR4 decreases adipose tissue hypertrophy and affects circulating adipokine levels in HFD obese mice.COH-SR4 prevents hepatic lipid accumulation and fatty liver in HFD obese mice. Animal Model:Nine-week old male C57BL/6J mice Dosage:5 mg/kg Administration:Oral gavage, three times a week, for 6 weeks Result:Decreased body weight and fat mass in HFD obese mice.

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Others

Other Targets

Others

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73439-19-7

350.02

C13H8Cl4N2O

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (357.11 mM)

Clc1cc(Cl)cc(NC(=O)Nc2cc(Cl)cc(Cl)c2)c1

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(-20℃)

With Ice Pack

≥ 2 years