Obeticholic Acid
(Synonyms: 奥贝胆酸; INT-747; 6-ECDCA; 6-Ethylchenodeoxycholic acid) 目录号 : GC14158
Obeticholic Acid（奥贝胆酸；INT-747；6-ECDCA；6-Ethylchenodeoxycholic acid）是一种有效的，选择性的和口服活性的法尼醇X受体（FXR ）激动剂，EC50为99nM。
Cas No.:459789-99-2
Sample solution is provided at 25 µL, 10mM.
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Obeticholic Acid (INT-747; 6-ECDCA; 6-Ethylchenodeoxycholic acid) is a potent, selective and orally active farnesoid X receptor(FXR) agonist with an EC50 of 99nM[1]. FXR is a ligand-dependent transcription factor belonging to the nuclear hormone receptor superfamily that plays an important role in bile acid, lipid metabolism, carbohydrate homeostasis and inflammatory response[2]. Obeticholic Acid is a semisynthetic hydrophobic bile acid analog used to treat primary biliary cholangitis(PBC) and non-alcoholic steatohepatitis(NASH)[3].
In vitro, treatment of HepG2, Huh7 and SNU-449 cells with Obeticholic Acid (0.01-100µM) for 72h significantly inhibited cell proliferation with IC50 values of 1.067μM, 1.038μM and 0.706μM, respectively, and also inhibited cell migration and invasion[4]. Treatment of primary cultures of human intrahepatic cholangiocarcinoma(iCCA) with Obeticholic Acid (0-2.5µM) for 3-10 days significantly inhibited the proliferation of mucinous and mixed iCCA cells and upregulated FXR gene expression[5].
In vivo, oral treatment of mice with NASH with Obeticholic Acid (10mg/kg) for 4 or 8 weeks significantly inhibited the number of hepatic coronary structures(hCLS), reduced the area of fibrosis and the mRNA expression of fibrotic genes, and long-term treatment had no effect on the body weight and adipose tissue weight of mice[6]. Oral treatment of rats with ascites cirrhosis with Obeticholic Acid (5mg/kg) for 2 weeks significantly reduced intestinal bacterial translocation, reduced intestinal immune cell infiltration, and normalized the expression of inflammatory cytokines[7].
References:
[1] Pellicciari R, Fiorucci S, Camaioni E, et al. 6α-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity[J]. Journal of medicinal chemistry, 2002, 45(17): 3569-3572.
[2] Shaik F B, Prasad D V R, Narala V R. Role of farnesoid X receptor in inflammation and resolution[J]. Inflammation Research, 2015, 64: 9-20.
[3] Chapman R W, Lynch K D. Obeticholic acid—a new therapy in PBC and NASH[J]. British medical bulletin, 2020, 133(1): 95-104.
[4] Attia Y M, Tawfiq R A, Ali A A, et al. The FXR agonist, obeticholic acid, suppresses HCC proliferation & metastasis: role of IL-6/STAT3 signalling pathway[J]. Scientific reports, 2017, 7(1): 12502.
[5] Di Matteo S, Nevi L, Costantini D, et al. The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma[J]. PLoS One, 2019, 14(1): e0210077.
[6] Goto T, Itoh M, Suganami T, et al. Obeticholic acid protects against hepatocyte death and liver fibrosis in a murine model of nonalcoholic steatohepatitis[J]. Scientific reports, 2018, 8(1): 8157.
[7] Úbeda M, Lario M, Muñoz L, et al. Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats[J]. Journal of hepatology, 2016, 64(5): 1049-1057.
Obeticholic Acid（奥贝胆酸；INT-747；6-ECDCA；6-Ethylchenodeoxycholic acid）是一种有效的，选择性的和口服活性的法尼醇X受体（FXR ）激动剂，EC50为99nM[1]。FXR是一种配体依赖性转录因子，属于核激素受体超家族，在胆汁酸、脂质代谢、碳水化合物稳态和炎症反应中发挥重要作用[2]。Obeticholic Acid是一种半合成疏水性胆汁酸类似物，用于治疗原发性胆汁性胆管炎（PBC）和非酒精性脂肪性肝炎（NASH）[3]。
在体外，Obeticholic Acid（0.01-100µM）处理肝癌细胞HepG2、Huh7和SNU-449细胞72h，显著抑制了细胞增殖，IC50值分别为1.067μM、1.038μM和0.706μM，还抑制了细胞迁移和侵袭[4]。Obeticholic Acid（0-2.5µM）处理人肝内胆管癌（iCCA）的原代培养物3-10d，显著抑制了粘液性和混合iCCA细胞的增殖，上调了FXR基因表达[5]。
在体内，Obeticholic Acid（10mg/kg）通过口服治疗NASH小鼠4周或8周，显著抑制了肝冠状结构（hCLS）的数量，减少纤维化面积和纤维化基因的mRNA表达，且长期治疗对小鼠的体重和脂肪组织重量没有影响[6]。Obeticholic Acid（5mg/kg）通过口服治疗腹水性肝硬化大鼠2周，显著减少了肠道细菌易位，减少肠道免疫细胞浸润，使炎性细胞因子表达正常化[7]。
| Cell experiment [1]: | |
Cell lines | HepG2, Huh7, and SNU-449 cells |
Preparation Method | 1.2 to 1.8×103 cells per well were seeded in 96-well plates and cultured overnight. Then, the cells were treated with 0.01-100μM of Obeticholic Acid, or DMSO. After 72h, MTT reagent was added to the cells in each well followed by incubation for 2h, and the absorbance was determined using a microplate reader. The effect of treatments on cell viability was presented as the percentage of the absorbance at 570nm from treated cells versus that from untreated control cells. |
Reaction Conditions | 0.01-100µM; 72h |
Applications | Obeticholic Acid reduced the proliferation rates of HepG2, Huh7, and SNU-449 cells with IC50 values of 1.067μM, 1.038μM, and 0.706μM, respectively. |
| Animal experiment [2]: | |
Animal models | MC4R-KO mice |
Preparation Method | 8-week-old MC4R-KO mice were fed Western diet(WD) for 20 weeks, and control WT mice were fed Standard diet(SD) for the same period. MC4R-KO mice fed WD for 6 weeks received a single intraperitoneal injection of CCl4 diluted 1:20 in olive oil at a dose of 0.2ml/kg. After the onset of non-alcoholic steatohepatitis(NASH) symptoms, MC4R-KO mice were gavaged once daily with 10mg/kg Obeticholic Acid or vehicle (0.5% carboxymethyl cellulose) for 4 or 8 weeks. At the end of the experiment, mice were sacrificed under intraperitoneal pentobarbital anesthesia. |
Dosage form | 10mg/kg; p.o. |
Applications | Obeticholic Acid treatment significantly inhibited the number of hepatic crown-like structure(hCLS) and reduced the fibrotic area and mRNA expression of fibrogenic genes. Long-term treatment with Obeticholic Acid had no effect on body weight and adipose tissue weight in MC4R-KO mice. |
References: [1]Attia Y M, Tawfiq R A, Ali A A, et al. The FXR agonist, obeticholic acid, suppresses HCC proliferation & metastasis: role of IL-6/STAT3 signalling pathway[J]. Scientific reports, 2017, 7(1): 12502. [2]Goto T, Itoh M, Suganami T, et al. Obeticholic acid protects against hepatocyte death and liver fibrosis in a murine model of nonalcoholic steatohepatitis[J]. Scientific reports, 2018, 8(1): 8157. | |
| Cas No. | 459789-99-2 | SDF | |
| 别名 | 奥贝胆酸; INT-747; 6-ECDCA; 6-Ethylchenodeoxycholic acid | ||
| 化学名 | (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 | ||
| Canonical SMILES | CCC1C2CC(CCC2(C3CCC4(C(C3C1O)CCC4C(C)CCC(=O)O)C)C)O | ||
| 分子式 | C26H44O4 | 分子量 | 420.63 |
| 溶解度 | ≥ 21.5mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3774 mL | 11.8869 mL | 23.7739 mL |
| 5 mM | 0.4755 mL | 2.3774 mL | 4.7548 mL |
| 10 mM | 0.2377 mL | 1.1887 mL | 2.3774 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet