Identification
- Summary
Chenodeoxycholic acid is a bile acid used for the treatment of primary biliary cirrhosis.
- Brand Names
- Chenodal
- Generic Name
- Chenodeoxycholic acid
- DrugBank Accession Number
- DB06777
- Background
Chenodeoxycholic acid (or Chenodiol) is an epimer of ursodeoxycholic acid (DB01586). Chenodeoxycholic acid is a bile acid naturally found in the body. It works by dissolving the cholesterol that makes gallstones and inhibiting production of cholesterol in the liver and absorption in the intestines, which helps to decrease the formation of gallstones. It can also reduce the amount of other bile acids that can be harmful to liver cells when levels are elevated.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Chenodeoxycholic acid (DB06777)
- Weight
- Average: 392.572
Monoisotopic: 392.292659768 - Chemical Formula
- C24H40O4
- Synonyms
- 3alpha,7alpha-Dihydroxy-5beta-cholanic acid
- 7α-hydroxylithocholic acid
- Acide chenodeoxycholique
- Acido chenodeoxicholico
- Acidum chenodeoxycholicum
- Anthropodeoxycholic acid
- Anthropodesoxycholic acid
- CDCA
- Chenic acid
- Chenocholic acid
- Chenodeoxycholate
- Chenodeoxycholic acid
- Chenodesoxycholic acid
- Chenodiol
- Gallodesoxycholic acid
Pharmacology
- Indication
Chenodiol is indicated for patients with radiolucent stones in well-opacifying gallbladders, in whom selective surgery would be undertaken except for the presence of increased surgical risk due to systemic disease or age. Chenodiol will not dissolve calcified (radiopaque) or radiolucent bile pigment stones.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Radiolucent cholesterol gallstones •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
It acts by reducing levels of cholesterol in the bile, helping gallstones that are made predominantly of cholesterol to dissolve. Chenodeoxycholic acid is ineffective with stones of a high calcium or bile acid content.
- Mechanism of action
Chenodiol suppresses hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid in an expanded bile acid pool. These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones in the presence of a gall-bladder visualized by oral cholecystography. Bile acids may also bind the the bile acid receptor (FXR) which regulates the synthesis and transport of bile acids.
Target Actions Organism UBile acid receptor otherHumans UNuclear receptor subfamily 1 group I member 2 Not Available Humans UG-protein coupled bile acid receptor 1 Not Available Humans UAldo-keto reductase family 1 member C2 substrateHumans - Absorption
Chenodiol is well absorbed from the small intestine.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Chenodiol is well absorbed from the small intestine and taken up by the liver where it is converted to its taurine and glycine conjugates and secreted in bile. At steady-state, an amount of chenodiol near the daily dose escapes to the colon and is converted by bacterial action to lithocholic acid. About 80% of the lithocholate is excreted in the feces; the remainder is absorbed and converted in the liver to its poorly absorbed sulfolithocholyl conjugates. During chenodiol therapy there is only a minor increase in biliary lithocholate, while fecal bile acids are increased three- to fourfold.
- Route of elimination
About 80% of its bacterial metabolite lithocholate is excreted in the feces.
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Hepatotoxic.
- Pathways
Pathway Category Zellweger Syndrome Disease Congenital Bile Acid Synthesis Defect Type II Disease 27-Hydroxylase Deficiency Disease Bile Acid Biosynthesis Metabolic Cerebrotendinous Xanthomatosis (CTX) Disease Familial Hypercholanemia (FHCA) Disease Congenital Bile Acid Synthesis Defect Type III Disease - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Chenodeoxycholic acid can be increased when it is combined with Abametapir. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Chenodeoxycholic acid. Acemetacin The metabolism of Acemetacin can be decreased when combined with Chenodeoxycholic acid. Acenocoumarol The risk or severity of bleeding and bruising can be increased when Acenocoumarol is combined with Chenodeoxycholic acid. Acetylsalicylic acid The risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Chenodeoxycholic acid. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Chenix (Sigma Tau)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Chenodeoxycholic Acid Leadiant Capsule 250 mg Oral Leadiant Gmb H 2020-12-16 Not applicable EU 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Chenodal Tablet, film coated 250 mg/1 Oral Manchester Pharmaceuticals 2009-10-01 Not applicable US 
Chenodal Tablet, film coated 250 mg/1 Oral Travere Therapeutics 2015-12-28 Not applicable US Chenodiol Tablet, film coated 250 mg/1 Oral Nexgen Pharma, Inc. 2009-10-22 Not applicable US Chenodiol Tablet, film coated 250 mg/1 Oral LGM Pharma Solutions, LLC 2009-10-22 Not applicable US
Categories
- ATC Codes
- A05AA01 — Chenodeoxycholic acid
- Drug Categories
- Alimentary Tract and Metabolism
- Bile Acid Preparations
- Bile acids and derivatives
- Bile Acids and Salts
- Bile and Liver Therapy
- Bile Therapy
- Cholanes
- Cholic Acids
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Fused-Ring Compounds
- Gastrointestinal Agents
- Steroids
- UGT2B7 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dihydroxy bile acids, alcohols and derivatives. These are compounds containing or derived from a bile acid or alcohol, and which bears exactly two carboxylic acid groups.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Bile acids, alcohols and derivatives
- Direct Parent
- Dihydroxy bile acids, alcohols and derivatives
- Alternative Parents
- 7-hydroxysteroids / 3-alpha-hydroxysteroids / Secondary alcohols / Cyclic alcohols and derivatives / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- 3-alpha-hydroxysteroid / 3-hydroxysteroid / 7-hydroxysteroid / Alcohol / Aliphatic homopolycyclic compound / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Cyclic alcohol / Dihydroxy bile acid, alcohol, or derivatives
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- bile acid, dihydroxy-5beta-cholanic acid (CHEBI:16755) / C24 bile acids, alcohols, and derivatives, Cholane and derivatives (C02528) / C24 bile acids, alcohols, and derivatives (LMST04010032)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 0GEI24LG0J
- CAS number
- 474-25-9
- InChI Key
- RUDATBOHQWOJDD-BSWAIDMHSA-N
- InChI
- InChI=1S/C24H40O4/c1-14(4-7-21(27)28)17-5-6-18-22-19(9-11-24(17,18)3)23(2)10-8-16(25)12-15(23)13-20(22)26/h14-20,22,25-26H,4-13H2,1-3H3,(H,27,28)/t14-,15+,16-,17-,18+,19+,20-,22+,23+,24-/m1/s1
- IUPAC Name
- (4R)-4-[(1R,3aS,3bR,4R,5aS,7R,9aS,9bS,11aR)-4,7-dihydroxy-9a,11a-dimethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-1-yl]pentanoic acid
- SMILES
- [H][C@@]1(CC[C@@]2([H])[C@]3([H])[C@H](O)C[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCC(O)=O
References
- Synthesis Reference
Henry Francis Frost, Fritz Fabian, Christopher James Sharpe, William Arthur Jones, "Process for preparing chenodeoxycholic acid." U.S. Patent US4022806, issued October, 1974.
US4022806- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0000518
- KEGG Drug
- D00163
- KEGG Compound
- C02528
- PubChem Compound
- 10133
- PubChem Substance
- 99443291
- ChemSpider
- 9728
- BindingDB
- 21674
- 2323
- ChEBI
- 16755
- ChEMBL
- CHEMBL240597
- ZINC
- ZINC000003914808
- PharmGKB
- PA165958403
- PDBe Ligand
- JN3
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Chenodeoxycholic_acid
- PDB Entries
- 2jn3 / 3o02 / 6hl1 / 6ie9 / 7svg / 8dml
- FDA label
- Download (190 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Basic Science Obesity, Severe 1 4 Completed Diagnostic Bileacid Malabsorption 1 4 Completed Diagnostic Bileacid Malabsorption / Gallstones 1 4 Completed Treatment Obesity, Severe 2 3 Completed Treatment CTX 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 250 MG Tablet, film coated Oral 250 mg/1 Capsule Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 168-171 Maeke, S. and Rambacher, P.; US. Patent 4,163,017; July 31,1979; assigned to Diamalt A.G. (Germany). water solubility 89.9 mg/L (at 20 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 4.15 SANGSTER (1993) - Predicted Properties
Property Value Source Water Solubility 0.0197 mg/mL ALOGPS logP 3.01 ALOGPS logP 3.71 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 4.6 Chemaxon pKa (Strongest Basic) -0.54 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 77.76 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 109.27 m3·mol-1 Chemaxon Polarizability 46.35 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9766 Blood Brain Barrier + 0.9288 Caco-2 permeable + 0.73 P-glycoprotein substrate Substrate 0.6648 P-glycoprotein inhibitor I Non-inhibitor 0.8737 P-glycoprotein inhibitor II Inhibitor 0.5368 Renal organic cation transporter Non-inhibitor 0.8537 CYP450 2C9 substrate Non-substrate 0.7818 CYP450 2D6 substrate Non-substrate 0.9115 CYP450 3A4 substrate Substrate 0.7407 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.9456 CYP450 2D6 inhibitor Non-inhibitor 0.9781 CYP450 2C19 inhibitor Non-inhibitor 0.9707 CYP450 3A4 inhibitor Non-inhibitor 0.8405 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9563 Ames test Non AMES toxic 0.8794 Carcinogenicity Non-carcinogens 0.9329 Biodegradation Not ready biodegradable 0.992 Rat acute toxicity 2.5624 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9622 hERG inhibition (predictor II) Non-inhibitor 0.7246
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 200.1895715 predictedDarkChem Lite v0.1.0 [M-H]- 197.2871715 predictedDarkChem Lite v0.1.0 [M-H]- 204.3790715 predictedDarkChem Lite v0.1.0 [M-H]- 202.13918 predictedDeepCCS 1.0 (2019) [M+H]+ 201.3469715 predictedDarkChem Lite v0.1.0 [M+H]+ 197.1617715 predictedDarkChem Lite v0.1.0 [M+H]+ 198.9391715 predictedDarkChem Lite v0.1.0 [M+H]+ 204.03456 predictedDeepCCS 1.0 (2019) [M+Na]+ 200.2497715 predictedDarkChem Lite v0.1.0 [M+Na]+ 194.1090715 predictedDarkChem Lite v0.1.0 [M+Na]+ 197.7362715 predictedDarkChem Lite v0.1.0 [M+Na]+ 209.90514 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Other
- General Function
- Zinc ion binding
- Specific Function
- Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxyla...
- Gene Name
- NR1H4
- Uniprot ID
- Q96RI1
- Uniprot Name
- Bile acid receptor
- Molecular Weight
- 55913.915 Da
References
- Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, Shan B: Identification of a nuclear receptor for bile acids. Science. 1999 May 21;284(5418):1362-5. [Article]
- Xu Y, Watanabe T, Tanigawa T, Machida H, Okazaki H, Yamagami H, Watanabe K, Tominaga K, Fujiwara Y, Oshitani N, Arakawa T: Bile acids induce cdx2 expression through the farnesoid x receptor in gastric epithelial cells. J Clin Biochem Nutr. 2010 Jan;46(1):81-6. doi: 10.3164/jcbn.09-71. Epub 2009 Dec 29. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Zinc ion binding
- Specific Function
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
- Gene Name
- NR1I2
- Uniprot ID
- O75469
- Uniprot Name
- Nuclear receptor subfamily 1 group I member 2
- Molecular Weight
- 49761.245 Da
References
- Katona BW, Cummins CL, Ferguson AD, Li T, Schmidt DR, Mangelsdorf DJ, Covey DF: Synthesis, characterization, and receptor interaction profiles of enantiomeric bile acids. J Med Chem. 2007 Nov 29;50(24):6048-58. Epub 2007 Oct 27. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- G-protein coupled bile acid receptor activity
- Specific Function
- Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of m...
- Gene Name
- GPBAR1
- Uniprot ID
- Q8TDU6
- Uniprot Name
- G-protein coupled bile acid receptor 1
- Molecular Weight
- 35247.795 Da
References
- Katona BW, Cummins CL, Ferguson AD, Li T, Schmidt DR, Mangelsdorf DJ, Covey DF: Synthesis, characterization, and receptor interaction profiles of enantiomeric bile acids. J Med Chem. 2007 Nov 29;50(24):6048-58. Epub 2007 Oct 27. [Article]
- Ishizawa M, Matsunawa M, Adachi R, Uno S, Ikeda K, Masuno H, Shimizu M, Iwasaki K, Yamada S, Makishima M: Lithocholic acid derivatives act as selective vitamin D receptor modulators without inducing hypercalcemia. J Lipid Res. 2008 Apr;49(4):763-72. doi: 10.1194/jlr.M700293-JLR200. Epub 2008 Jan 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
- Specific Function
- Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent...
- Gene Name
- AKR1C2
- Uniprot ID
- P52895
- Uniprot Name
- Aldo-keto reductase family 1 member C2
- Molecular Weight
- 36734.97 Da
References
- Stolz A, Hammond L, Lou H, Takikawa H, Ronk M, Shively JE: cDNA cloning and expression of the human hepatic bile acid-binding protein. A member of the monomeric reductase gene family. J Biol Chem. 1993 May 15;268(14):10448-57. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Catalyzes the first step in the oxidation of the side chain of sterol intermediates; the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol. Has also a vitamin D3-25-hydroxylase a...
- Gene Name
- CYP27A1
- Uniprot ID
- Q02318
- Uniprot Name
- Sterol 26-hydroxylase, mitochondrial
- Molecular Weight
- 60234.28 Da
References
- Matsuzaki Y, Bouscarel B, Ikegami T, Honda A, Doy M, Ceryak S, Fukushima S, Yoshida S, Shoda J, Tanaka N: Selective inhibition of CYP27A1 and of chenodeoxycholic acid synthesis in cholestatic hamster liver. Biochim Biophys Acta. 2002 Nov 20;1588(2):139-48. [Article]
- Bjorkhem I: Inborn errors of metabolism with consequences for bile acid biosynthesis. A minireview. Scand J Gastroenterol Suppl. 1994;204:68-72. [Article]
- Bjorkhem I, Araya Z, Rudling M, Angelin B, Einarsson C, Wikvall K: Differences in the regulation of the classical and the alternative pathway for bile acid synthesis in human liver. No coordinate regulation of CYP7A1 and CYP27A1. J Biol Chem. 2002 Jul 26;277(30):26804-7. Epub 2002 May 13. [Article]
- Keren Z, Falik-Zaccai TC: Cerebrotendinous xanthomatosis (CTX): a treatable lipid storage disease. Pediatr Endocrinol Rev. 2009 Sep;7(1):6-11. [Article]
- Honda A, Salen G, Matsuzaki Y, Batta AK, Xu G, Hirayama T, Tint GS, Doy M, Shefer S: Disrupted coordinate regulation of farnesoid X receptor target genes in a patient with cerebrotendinous xanthomatosis. J Lipid Res. 2005 Feb;46(2):287-96. Epub 2004 Dec 1. [Article]
- Goodwin B, Gauthier KC, Umetani M, Watson MA, Lochansky MI, Collins JL, Leitersdorf E, Mangelsdorf DJ, Kliewer SA, Repa JJ: Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):223-8. Epub 2002 Dec 30. [Article]
- Honda A, Salen G, Matsuzaki Y, Batta AK, Xu G, Leitersdorf E, Tint GS, Erickson SK, Tanaka N, Shefer S: Differences in hepatic levels of intermediates in bile acid biosynthesis between Cyp27(-/-) mice and CTX. J Lipid Res. 2001 Feb;42(2):291-300. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Deo AK, Bandiera SM: Identification of human hepatic cytochrome p450 enzymes involved in the biotransformation of cholic and chenodeoxycholic acid. Drug Metab Dispos. 2008 Oct;36(10):1983-91. doi: 10.1124/dmd.108.022194. Epub 2008 Jun 26. [Article]
- Gnerre C, Blattler S, Kaufmann MR, Looser R, Meyer UA: Regulation of CYP3A4 by the bile acid receptor FXR: evidence for functional binding sites in the CYP3A4 gene. Pharmacogenetics. 2004 Oct;14(10):635-45. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Glucuronosyltransferase activity
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60694.12 Da
References
- Lu Y, Heydel JM, Li X, Bratton S, Lindblom T, Radominska-Pandya A: Lithocholic acid decreases expression of UGT2B7 in Caco-2 cells: a potential role for a negative farnesoid X receptor response element. Drug Metab Dispos. 2005 Jul;33(7):937-46. Epub 2005 Apr 8. [Article]
Drug created at September 14, 2010 16:21 / Updated at February 21, 2021 18:52