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Rifaximin (Xifaxan)

现货
Catalog No.
A8512
RNA合成抑制剂,PXR激活剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
500mg
¥ 530.00
现货
1g
¥ 710.00
现货

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Background

Rifaximin, a rifamycin derivative, is a nonabsorbable antibiotic. Rifaximin inhibits RNA synthesis by binding the β subunit of the bacterial DNA-dependent RNA polymerase.

In vitro:Rifaximin, a gut-specific ligand for the human nuclear receptor pregnane-X receptor (PXR), contributes to the maintenance of the intestinal immune homeostasis. Rifaximin abrogates the binding of NF-κB caused by LPS. In human colon biopsies from inflammatory bowel diseases patients, exposure of rifaximin (100 μM) reduced mRNA levels of IL-8, Rantes, MIP-3α and TNFα induced by LPS stimulation [1]. Rifaximin acted on the β subunit of the deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase enzyme of bacteria to inhibit bacterial RNA synthesis. The susceptibility of Gram-positive organisms to rifaximin was greater than that of Gram-negative organisms [2]. In the DPX2 cell line transfected with stable recombinant human PXR expression, hPXR was significantly activated at RIFax concentrations over 1 μM and the EC50 was about 20 μM[3].

In vivo:In the small intestine of hPXR mice treated with rifaximin, several PXR target genes such as CYP3A11, GSTA1, MRP2, and OATP2 were up-regulated. Rifaximin treatment demonstrated no significant effect on hepatic PXR target genes in wild-type, Pxr-null, and hPXR mice [3]. In PXR-humanized mice, long-term administration of rifaximin for 6 months on the liver up-regulated the expression of hepatic genes related to triglyceride synthesis and lipid accumulation [4].

Clinical trials: Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy effectively. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy [5]. Among patients with irritable bowel syndrome (IBS) without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms, bloating, abdominal pain, and loose or watery stools [6]. Rifaximin could improve the symptom in IBS patients, such as abdominal bloating and flatulence [7].

References:
[1].  Mencarelli A, Renga B, Palladino G, et al. Inhibition of NF-κB by a PXR-dependent pathway mediates counter-regulatory activities of rifaximin on innate immunity in intestinal epithelial cells[J]. European journal of pharmacology, 2011, 668(1): 317-324.
[2].  Gillis J C, Brogden R N. Rifaximin[J]. Drugs, 1995, 49(3): 467-484.
[3].  Ma X, Shah Y M, Guo G L, et al. Rifaximin is a gut-specific human pregnane X receptor activator[J]. Journal of Pharmacology and Experimental Therapeutics, 2007, 322(1): 391-398.
[4].  Cheng J, Krausz K, Tanaka N, et al. Chronic exposure to rifaximin causes hepatic steatosis in pregnane X receptor-humanized mice[J]. Toxicological Sciences, 2012: kfs211.
[5].  Bass N M, Mullen K D, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy[J]. New England Journal of Medicine, 2010, 362(12): 1071-1081.
[6].  Pimentel M, Lembo A, Chey W D, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation[J]. New england journal of medicine, 2011, 364(1): 22-32.
[7].  Sharara A I, Aoun E, Abdul-Baki H, et al. A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence[J]. The American journal of gastroenterology, 2006, 101(2): 326-333.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt785.88
Cas No.80621-81-4
FormulaC43H51N3O11
Solubility≥83.3mg/mL in DMSO
SDFDownload SDF
Canonical SMILESO[C@@H]([C@H](C)[C@H]([C@H](/C=C/C=C(C)\C(NC1=C2O)=O)C)O)[C@@H](C)[C@@H]([C@H](C)[C@H](/C=C/O[C@@](C3=O)(C)OC4=C3C(C5=C1N(C=CC(C)=C6)C6=N5)=C2C(O)=C4C)OC)OC(C)=O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

CRL1831细胞

制备方法

在DMSO中的溶解度大于39.3mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

50 μM;3小时

实验结果

Rifaximin抑制LPS诱导的NF-κB DNA结合活性,从而下调细胞因子与趋化因子的表达。此外,Rifaximin也增加经LPS诱导后PXR和NF-κB p65之间的物理结合程度。

动物实验 [2]:

动物模型

hPXR小鼠

给药剂量

1 mg/kg/day;口服给药;6个月

实验结果

在hPXR小鼠中,Rifaximin呈时间依赖性地逐渐改善肝细胞脂肪变性,同时,不会引起结节性增生。此外,与接受Rifaximin治疗1周的hPXR小鼠相比,接受Rifaximin治疗1个月、3个月和6个月的hPXR小鼠的血清甘油三酯和血清游离脂肪酸显著降低。然而,接受Rifaximin治疗1周、1个月、3个月和6个月的hPXR小鼠的血清ALT和AST活性无显著差异。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Mencarelli A, Renga B, Palladino G, et al. Inhibition of NF-κB by a PXR-dependent pathway mediates counter-regulatory activities of rifaximin on innate immunity in intestinal epithelial cells[J]. European journal of pharmacology, 2011, 668(1): 317-324.

[2]. Cheng J, Krausz K, Tanaka N, et al. Chronic exposure to rifaximin causes hepatic steatosis in pregnane X receptor-humanized mice[J]. Toxicological Sciences, 2012: kfs211

质量控制

化学结构

Rifaximin (Xifaxan)