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SR12813

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Chemical Structure| 126411-39-0 同义名 : GW 485801
CAS号 : 126411-39-0
货号 : A148389
分子式 : C24H42O7P2
纯度 : 99%+
分子量 : 504.534
MDL号 : MFCD00888473
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(99.1 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyzes the conversion of HMG-CoA to mevalonate, a four-electron oxidoreduction that is the rate-limiting step in the synthesis of cholesterol and other isoprenoids[3]. SR-12813 inhibits cholesterol biosynthesis in Hep G2 cells via an enhanced degradation of HMG-CoA reductase. After 7 days plasma cholesterol was decreased by 15% in the 10 mg/kg/day group and by 19% in the 25 mg/kg/day group[4]. SR-12813 inhibited incorporation of tritiated water into cholesterol with an IC50 of 1.2 mM but had no effect on fatty acid synthesis. Furthermore, SR-12813 reduced cellular HMG-CoA reductase activity with an IC50 of 0.85 mM. The inhibition of HMG-CoA reductase activity was rapid with a T1/2 of 10 min. After a 16-h incubation with SR-12813, mRNA levels of HMG-CoA reductase and low density lipoprotein (LDL) receptor were increased. The increased expression of LDL receptor translated into a higher LDL uptake, which can explain the primary hypocholesterolemic effect of SR-12813 in vivo[5]. Treatment of hCMEC/D3 cells for 72 hr with rifampin or SR12813 (two well-established hPXR ligands) or PIs (atazanavir or ritonavir) resulted in an increase in P-gp expression by 1.8-, 6-, and 2-fold, respectively, with no effect observed for MRP1 expression[6]. Preactivation of hPXR by SR12813 in MDA-MB-231 cells led to an increased resistance to Taxol at concentrations of 20 and 50 nM[7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.98mL

0.40mL

0.20mL

9.91mL

1.98mL

0.99mL

19.82mL

3.96mL

1.98mL
参考文献

[1]Jones SA, Moore LB, et al. The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol. 2000 Jan;14(1):27-39.

[2]Berkhout TA, Simon HM, et al. The novel cholesterol-lowering drug SR-12813 inhibits cholesterol synthesis via an increased degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem. 1996 Jun 14;271(24):14376-82.

[3]Jon A Friesen,et al. The 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductases. Genome Biol. 2004;5(11):248.

[4] T A Berkhout,et al. SR-12813 lowers plasma cholesterol in beagle dogs by decreasing cholesterol biosynthesis. Atherosclerosis. 1997 Sep;133(2):203-12.

[5]Berkhout T, et al. The novel cholesterol-lowering drug SR-12813 inhibits cholesterol synthesis via an increased degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem. 1996 Jun 14;271(24):14376-82.

[6]Jason A Zastre,et al. Up-regulation of P-glycoprotein by HIV protease inhibitors in a human brain microvessel endothelial cell line. J Neurosci Res. 2009 Mar;87(4):1023-36.

[7]Yakun Chen,et al. Regulation of drug resistance by human pregnane X receptor in breast cancer. Cancer Biol Ther. 2009 Jul;8(13):1265-72.