Obeticholic Acid
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Obeticholic Acid (6alpha-ethyl-chenodeoxycholic acid, 6-ECDCA, INT-747) 是一种有效的和选择性的FXR激动剂,EC50值为99 nM[1]。
法尼醇X 受体(farnesoid X receptor,FXR)是一个核受体,参与胆汁酸的动态平衡,肝纤维化,肝脏和肠道炎症以及心血管疾病[2]。
Obeticholic Acid是一种有效的和选择性的FXR激动剂,具有抗胆汁淤积活性[1]。Obeticholic Acid是半合成胆汁酸衍生物和有效的FXR配体。在雌激素诱导的胆汁淤积大鼠中,6-ECDCA防止17α-乙炔雌二醇(E217α)诱导的胆汁淤积[2]。在肝硬化门脉高压(PHT)大鼠模型中,INT-747 (30 mg/kg)重新激活FXR下游的信号通路,通过降低肝内总血管阻力(IHVR)从而降低门静脉压力,不会产生有害的全身性低血压。这种效应与增加的eNOS活性相关联[3]。在盐敏感高血压和胰岛素抗性(IR)Dahl大鼠模型中,高盐(HS)饮食显著增加全身血压和下调组织DDAH的表达。INT-747增强胰岛素的敏感性,抑制DDAH表达的下降[4]。
参考文献:
[1]. Pellicciari R, Fiorucci S, Camaioni E, et al. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem, 2002, 45(17): 3569-3572.
[2]. Fiorucci S, Clerici C, Antonelli E, et al. Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis. J Pharmacol Exp Ther, 2005, 313(2): 604-612.
[3]. Verbeke L, Farre R, Trebicka J, et al. Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats. Hepatology, 2014, 59(6): 2286-2298.
[4]. Ghebremariam YT, Yamada K, Lee JC, et al. FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats. PLoS One, 2013, 8(4): e60653.
- 1. Dipankar Bhattacharya, Christine Becker, et al. "Repositioning of a Novel GABA-B Receptor Agonist, AZD3355 (Lesogaberan), for the Treatment of Non-alcoholic Steatohepatitis." Sci Rep. 2021 Oct 21;11(1):20827. PMID:34675338
- 2. Morshead ML, Sedore CA, et al. "Caenorhabditis Intervention Testing Program: the farnesoid X receptor agonist obeticholic acid does not robustly extend lifespan in nematodes." MicroPubl Biol. 2020;2020:10.17912/micropub.biology.000257. PMID:32550518
- 3. Selina Costa. "Characterizing a Novel Ligand for the Farnesoid X Receptor using Transgenic Zebrafish." University of Toronto. Jun-2018.
- 4. Kent, Rebecca. "Effects of Fenofibrate on CYP2D6 and Regulation of ANG1 and RNASE4 by the FXR Agonist Obeticholic Acid." indigo.uic.edu.2017.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 420.63 |
Cas No. | 459789-99-2 |
Formula | C26H44O4 |
Solubility | ≥21.5 mg/mL in DMSO; insoluble in H2O; ≥21.3 mg/mL in EtOH |
Chemical Name | (4R)-4-[(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid |
SDF | Download SDF |
Canonical SMILES | CCC1C2CC(CCC2(C3CCC4(C(C3C1O)CCC4C(C)CCC(=O)O)C)C)O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验 [1]: | |
细胞系 |
大鼠肝细胞 |
制备方法 |
溶解度有限。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃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℃可放置数月。 |
反应条件 |
24 h |
实验结果 |
在大鼠肝细胞中,Obeticholic acid反式激活FXR并调节FXR调节基因,导致Shp和bsep mRNA表达增加3至5倍,FXR配体处理后,cyp7a1、cyp8b1和ntcp的mRNA表达降低50至70%。 |
动物实验 [2]: | |
动物模型 |
雄性Wistar大鼠,重量200-250 g |
给药剂量 |
30 mg/kg |
制备方法 |
溶于0.75-1.0 mL新鲜制备的甲基纤维素(1%) |
实验结果 |
Obeticholic acid可以重新激活下游FXR信号通路并减少硫代乙酰胺(TAA)和胆管结扎(BDL)模型中的PP,而不影响全身血液动力学。它还恢复实验性肝硬化中内皮功能,减少总IHVR。 |
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. Fiorucci S, Clerici C, Antonelli E et al. Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis. J Pharmacol Exp Ther. 2005 May;313(2):604-12. Epub 2005 Jan 11. 2. Verbeke L, Farre R, Trebicka J et al. Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats. Hepatology. 2014 Jun;59(6):2286-98. |
质量控制和MSDS
- 批次: