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
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.
Safety
- HS Code
- 2918199890
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.
N-Bromosuccinimide Price
- Product number
- SML3096
- Product name
- Obeticholic acid
- Purity
- ≥98% (HPLC)
- Packaging
- 5MG
- Price
- $89
- Updated
- 2024/03/01
- Product number
- SML3096
- Product name
- Obeticholic acid
- Purity
- ≥98% (HPLC)
- Packaging
- 25MG
- Price
- $359
- Updated
- 2024/03/01
- Product number
- CDS024140
- Product name
- 6-Ethylchenodeoxycholic acid
- Packaging
- 25mg
- Price
- $391
- Updated
- 2024/03/01
- Product number
- E899810
- Product name
- 6-Ethylchenodeoxycholic acid
- Packaging
- 100mg
- Price
- $495
- Updated
- 2021/12/16
- Product number
- E899810
- Product name
- 6-Ethylchenodeoxycholic acid
- Packaging
- 5mg
- Price
- $55
- Updated
- 2021/12/16
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
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View Lastest Price from Obeticholic Acid manufacturers
- 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
- Product
- Obeticholic Acid 459789-99-2
- Price
- US $1.00-1.00/Kg/Bag
- Min. Order
- 1g
- Purity
- 99%
- Supply Ability
- 50tons
- Release date
- 2020-04-30
- Product
- Obeticholic Acid 459789-99-2
- Price
- US $7.00/KG
- Min. Order
- 25KG
- Purity
- 98%
- Supply Ability
- 200 ton
- Release date
- 2023-09-07