obeticholic acid   Click here for help

GtoPdb Ligand ID: 3435

Synonyms: 6-ECDCA | 6-Et CDCA | 6-ethylchenodeoxycholic acid | INT-747 | OCA | Ocaliva®
Approved drug PDB Ligand
obeticholic acid is an approved drug (EMA & FDA (2016))
Compound class: Synthetic organic
Comment: Obeticholic acid is a semisynthetic bile acid analogue. It acts as a farnesoid X receptor (FXR) agonist.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

obeticholic acid is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 77.76
Molecular weight 420.32
XLogP 7.04
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CCC1C(O)C2C3CCC(C3(C)CCC2C2(C1CC(O)CC2)C)C(CCC(=O)O)C
Isomeric SMILES CC[C@H]1[C@@H](O)[C@H]2[C@@H]3CC[C@@H]([C@@]3(C)CC[C@@H]2[C@@]2([C@H]1C[C@H](O)CC2)C)[C@@H](CCC(=O)O)C
InChI InChI=1S/C26H44O4/c1-5-17-21-14-16(27)10-12-26(21,4)20-11-13-25(3)18(15(2)6-9-22(28)29)7-8-19(25)23(20)24(17)30/h15-21,23-24,27,30H,5-14H2,1-4H3,(H,28,29)/t15-,16-,17-,18-,19+,20+,21+,23+,24-,25-,26-/m1/s1
InChI Key ZXERDUOLZKYMJM-ZWECCWDJSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
In March 2014 the EMA granted orphan designation for obeticholic acid for the treatment of primary sclerosing cholangitis. Also in 2014, the US FDA granted Fast Track designation to obeticholic acid (OCA) for the treatment of primary biliary cirrhosis. The Fast Track programme is intended to expedite the development, review and potential approval of drugs which treat serious conditions and fill an unmet medical need. In May 2016, the US FDA granted full marketing authorisation for obeticholic acid to be used for the treatment of primary biliary cholangitis.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Obeticholic acid is a farnesoid X receptor (FXR) agonist which has anticholestatic activity in an in vivo rat model of cholestasis [3]. FXR is a nuclear receptor for bile acids [2] and is important for the regulation of expression of target genes involved in bile acid and cholesterol homeostasis. Ligand activation of FXR has two noteworthy effects; repression of the production of bile acid biosynthetic enzymes and enhanced expression of proteins involved in bile acid transport. These effects account for the compound's anticholestatic activity [1].
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)