Description Indications and Usage Mechanisms of Action Clinical Research References
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Obeticholic Acid

Description Indications and Usage Mechanisms of Action Clinical Research References
Product Name
Obeticholic Acid
CAS No.
459789-99-2
Chemical Name
Obeticholic Acid
Synonyms
6-Ethylchenodeoxycholic acid;Ocaliva;(R)-4-((3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid;9470;1osv;6alph;C15636;6-Ecdca;CS-1441;pha,7aL
CBNumber
CB92484652
Molecular Formula
C26H44O4
Formula Weight
420.63
MOL File
459789-99-2.mol
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Obeticholic Acid Property

Melting point:
108-110 °C
Boiling point:
562.9±25.0 °C(Predicted)
Density 
1.091
storage temp. 
-20°C
solubility 
Soluble in DMSO (up to 35 mg/ml) or in Ethanol (up to 25 mg/ml)
form 
White solid.
pka
4.76±0.10(Predicted)
color 
White
Stability:
Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 2 months.
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Safety

HS Code 
2918199890
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
SML3096
Product name
Obeticholic acid
Purity
≥98% (HPLC)
Packaging
5MG
Price
$89
Updated
2024/03/01
Sigma-Aldrich
Product number
SML3096
Product name
Obeticholic acid
Purity
≥98% (HPLC)
Packaging
25MG
Price
$359
Updated
2024/03/01
Sigma-Aldrich
Product number
CDS024140
Product name
6-Ethylchenodeoxycholic acid
Packaging
25mg
Price
$391
Updated
2024/03/01
TRC
Product number
E899810
Product name
6-Ethylchenodeoxycholic acid
Packaging
100mg
Price
$495
Updated
2021/12/16
TRC
Product number
E899810
Product name
6-Ethylchenodeoxycholic acid
Packaging
5mg
Price
$55
Updated
2021/12/16
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Obeticholic Acid Chemical Properties,Usage,Production

Description

Obeticholic acid is a semi-synthetic bile acid analogue and acts as a farnesoid-X receptor (FXR) agonist. It is used for the treatment of primary biliary cholangitis. It is also under investigation for the treatment of other liver diseases,primary biliary cirrhosis, bile acid diarrhea and related disorders. Study has shown that it also has potential for treating nonalcoholicsteatohepatitis (NASH), and portal hypertension. Obeticholic acid takes effect through acting s the agonist of the farnesoid X receptor (FXR), which is the regulator of bile and cholesterol metabolism in the liver. 

Indications and Usage

Obeticholic acid is also called 6-Ethylchenodeoxycholic acid. It is a new derivative of chenodeoxycholic acid (CDCA) in human primary bile acids, a natural ligand for farnesoid x receptors (FXR). Obeticholic acid was developed by American pharmaceutical company Intercept as the first drug to treat cholestatic liver disease in 20 years, and it is administered on patients that do not respond well to or cannot tolerate the old standard treatment drug ursodeoxycholic acid. Obeticholic acid has also been tested to treat a more common form of fatty liver – non-alcoholic fatty liver disease (NAFLD). Obeticholic acid can also be developed to treat other liver and intestine diseases.

Mechanisms of Action

Obeticholic acid belongs to FXR stimulants, activating FXRs and indirectly inhibiting Cytochrome P450 Family 7 Subfamily A Member 1 (CYP7A1) expression. As CYP7A1 is a rate-limiting enzyme of bile acid biosynthesis, obeticholic acid can inhibit the bile acid synthesis and is used to treat primary biliary cirrhosis.

Clinical Research

In a placebo control phase III clinical trial, Obeticholic acid increased levels of two biomarkers indicating lowered risk in liver transplant. The composite end point of the clinical research is that alkaline phosphatase lowered by at least 15%, serum alkaline phosphatase activity was 1.67 times lower than the normal upper limit, and bilirubin levels were within normal range; alkaline phosphatase is a biomarker indicating liver disease severity. An American 6-week, multi-center, randomized, and double-blind clinical trial included 64 cases of type 2 diabetes patients with NAFLD, and it proved that Obeticholic acid not only increased insulin sensitivity, but also improved liver inflammation and fibrosis levels, and it has certain weight-reducing effects. However, this conclusion requires further investigation with a larger and more long-term follow-up, as well as scientific backing in liver pathology.

References

Verbeke, L, et al. "Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats."Hepatology 59.6(2014):2286-98.
Silveira, M. G., and K. D. Lindor. "Obeticholic acid and budesonide for the treatment of primary biliary cirrhosis." Expert Opinion on Pharmacotherapy 15.3(2014):365.

Description

Obeticholic acid is a potent and selective farnesoid X receptor agonist that promotes the flow of bile in the liver. The drug was approved by the USFDA for the treatment of the rare chronic liver disease primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with inadequate response to UDCA or as a single agent therapy in adults unable to tolerate UDCA. Obeticholic acid was discovered at the Università de Perugia and developed by Intercept Pharmaceuticals. Obeticholic acid has also been granted orphan drug designation for the treatment of primary sclerosing cholangitis and primary biliary cirrhosis and has received breakthrough therapy designation for the treatment of patients with nonalcohol steatohepatitis (NASH) with liver fibrosis.

Uses

6-Ethylchenodeoxycholic Acid is a derivative of the bile acid Chenodeoxycholic Acid (C291900). 6-Ethylchenodeoxycholic Acid is a potent activator of the farnesoid X nuclear receptor which reduces liver fat and fibrosis in animal models of fatty liver disease.

Definition

ChEBI: A dihydroxy-5beta-cholanic acid that is chenodeoxycholic acid carrying an additional ethyl substituent at the 6alpha-position. A semi-synthetic bile acid which acts as a farnesoid X receptor agonist and is used for treatme t of primary biliary cholangitis.

Synthesis

The synthesis of obeticholic acid was initiated from commercial 3|á-hydroxy-7-keto-5|?-cholan-24-oic acid (138). Fischer esterification of 138 provided methyl ester 139, which was treated with trimethylsilyl chloride and triethylamine to protect the secondary alcohol. Reaction of the protected alcohol with lithium diisopropylamine and trimethylsilyl chloride gave silyl enol ether 140. Aldol condensation with acetaldehyde and boron trifluoride etherate followed by saponification of the methyl ester produced enone 141. Hydrogenation of the olefin followed by heating to reflux to epimerize the resulting ethyl group produced the |á-ethyl ketone 142 in 62% yield from compound 138. Reduction of the ketone in 142 with sodium borohydride and subsequent crystallization from phosphoric acid and water gave obeticholic acid (XIV) in 90% yield.

Enzyme inhibitor

This semisynthetic bile acid analogue (FW = 420.63 g/mol; CAS 459789- 99-2), also named INT-747, 6α-ethyl-chenodeoxycholate, and (3α,5β,6α, 7α)-6-ethyl-3,7-dihydroxycholan-24-oic acid, is an analogue of the naturally occurring bile acid (FW = 392.57 g/mol; CAS 474-25-9). The latter is synthesized in the liver, where it conjugated to form taurochenodeoxycholate and glycol-chenodeoxycholate, reducing its pKa and increasing retention in the gastrointestinal tract, until reabsorption by the ileum. Chenodeoxycholate is the most active physiological ligand known for the farnesoid X receptor, or FXR (encoded by the NR1H4 gene in humans) that translocates to the nucleus, dimerizes, and binds to hormone response elements. Obeticholic acid reduces bacterial translocation and invasion in cirrhotic rats by restoring intestinal barrier integrity (through increased expression of tight junction proteins) and by inhibiting inflammation. Obeticholate likewise up-regulated expression of the FXR-associated gene small heterodimer partner (SHP).

storage

+4°C

References

1) Fiorucci?et al.?(2005),?Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis; J. Pharmacol. Exp. Ther.,?313?604 2) Rizzo?et al. (2006),?The farnesoid X receptor promotes adipocyte differentiation and regulates adipose cell function in vivo;?Mol. Pharmacol.,?70?1164 3) Maneschi?et al.?(2013),?FXR activation normalizes insulin sensitivity in visceral preadipocytes of a rabbit model of MetS; J. Endocrinol.,?218?215 4) Carr and Reid (2015),?FXR agonists as therapeutic agents for non-alcoholic fatty liver disease; Curr. Atheroscler. Rep,?17?500 5) Jahn?et al. (2016),?Non-Alcoholic Steatohepatitis: From Pathophysiology to Novel Therapies; Dig. Dis.,?34?356 6) Hirschfield?et al. (2015),?Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid; Gastroenterology,?148?751

Obeticholic Acid Preparation Products And Raw materials

Raw materials

Preparation Products

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Obeticholic Acid Suppliers

CHANGZHOU PHARMACEUTICAL FACTORY
Tel
519-88821493 18915891730
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shm@czpharma.com
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China
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163
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Xiamen Halosyntech Co., Ltd
Tel
0592-6688068 18106901346
Fax
0592-6686768
Email
qbl2015@halolife.cn
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China
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INTERCHEMIE NANJING PHARMATECH CO., LTD
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13656237714 13656237714
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0512-65852853
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xiaokunfu@kyyykj.com
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China
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Shanghai Mixiu Chemical Co., Ltd.
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18101936766
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021-58583907
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eileen@shmychem.com
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China
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NANJING ZENJI PHARMACEUTICALS
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025-58231105-8151
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025-83172562
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marketing@zenjipharma.com
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Jiangsu Vcare PharmaTech Co., Ltd.
Tel
13327700685
Fax
+86-25-58744115
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sales@vcarepharmatech.com
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China
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Jinan Baozhao Pharmaceutical Technology Co., Ltd.
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0531-82371868 13210529039
Fax
0531-82371858
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baozhaopharm@163.com
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China
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TargetMol Chemicals Inc.
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021-021-33632979 15002134094
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021-33632979
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marketing@targetmol.com
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China
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7783
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Shanghai jerryxing Biomedical Technology Co., Ltd
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17721492509
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643638326@qq.com
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Chemvon Biotechnology Co., Ltd
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021-50790412
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+86-21-50790419
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info@chemvon.com
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View Lastest Price from Obeticholic Acid manufacturers

Sinoway Industrial co., ltd.
Product
Obeticholic Acid 459789-99-2
Price
US $0.00/Kg/Bag
Min. Order
2Kg/Bag
Purity
99% up, High Density
Supply Ability
20 tons
Release date
2022-08-11
WUHAN FORTUNA CHEMICAL CO., LTD
Product
Obeticholic Acid 459789-99-2
Price
US $0.00/Kg/Bag
Min. Order
10g
Purity
98%-102%
Supply Ability
500G
Release date
2021-07-15
Hebei Weibang Biotechnology Co., Ltd
Product
Obeticholic Acid 459789-99-2
Price
US $10.00/KG
Min. Order
1KG
Purity
99%
Supply Ability
10 mt
Release date
2024-12-04

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