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Identification
NameChenodeoxycholic acid
Accession NumberDB06777
TypeSmall Molecule
GroupsApproved
Description

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.

Structure
Thumb
Synonyms
3alpha,7alpha-Dihydroxy-5beta-cholanic acid
7alpha-Hydroxylithocholic acid
Anthropodeoxycholic acid
Anthropodesoxycholic acid
CDCA
Chenic acid
Chenix
Chenocholic acid
Chenodeoxycholic acid
Chenodesoxycholic acid
Chenodiol
Gallodesoxycholic acid
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Chenodaltablet, film coated250 mg/1oralRetrophin, Inc.2015-12-28Not applicableUs
Chenodaltablet, film coated250 mg/1oralManchester Pharmaceuticals Inc.2009-10-01Not applicableUs
Chenodioltablet, film coated250 mg/1oralNexgen Pharma, Inc.2009-10-01Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ChenixSigma Tau
Brand mixturesNot Available
SaltsNot Available
Categories
UNII0GEI24LG0J
CAS number474-25-9
WeightAverage: 392.572
Monoisotopic: 392.292659768
Chemical FormulaC24H40O4
InChI KeyInChIKey=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-[(1S,2S,5R,7S,9R,10R,11S,14R,15R)-5,9-dihydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-14-yl]pentanoic acid
SMILES
[H][C@@]1(CC[C@@]2([H])[C@]3([H])[[email protected]](O)C[C@]4([H])C[[email protected]](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[[email protected]](C)CCC(O)=O
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassBile acids, alcohols and derivatives
Direct ParentDihydroxy bile acids, alcohols and derivatives
Alternative Parents
Substituents
  • Dihydroxy bile acid, alcohol, or derivatives
  • 7-hydroxysteroid
  • 3-alpha-hydroxysteroid
  • Hydroxysteroid
  • 3-hydroxysteroid
  • Cyclic alcohol
  • Secondary alcohol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationChenodiol 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.
PharmacodynamicsIt 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 actionChenodiol 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.
Related Articles
AbsorptionChenodiol is well absorbed from the small intestine.
Volume of distributionNot Available
Protein bindingNot 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 eliminationAbout 80% of its bacterial metabolite lithocholate is excreted in the feces.
Half lifeNot Available
ClearanceNot Available
ToxicityHepatotoxic.
Affected organismsNot Available
Pathways
PathwayCategorySMPDB ID
Cerebrotendinous Xanthomatosis (CTX)DiseaseSMP00315
27-Hydroxylase DeficiencyDiseaseSMP00720
Bile Acid BiosynthesisMetabolicSMP00035
Familial Hypercholanemia (FHCA)DiseaseSMP00317
Congenital Bile Acid Synthesis Defect Type IIDiseaseSMP00314
Zellweger SyndromeDiseaseSMP00316
Congenital Bile Acid Synthesis Defect Type IIIDiseaseSMP00318
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9766
Blood Brain Barrier+0.9288
Caco-2 permeable+0.73
P-glycoprotein substrateSubstrate0.6648
P-glycoprotein inhibitor INon-inhibitor0.8737
P-glycoprotein inhibitor IIInhibitor0.5368
Renal organic cation transporterNon-inhibitor0.8537
CYP450 2C9 substrateNon-substrate0.7818
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.7407
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9456
CYP450 2D6 inhibitorNon-inhibitor0.9781
CYP450 2C19 inhibitorNon-inhibitor0.9707
CYP450 3A4 inhibitorNon-inhibitor0.8405
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9563
Ames testNon AMES toxic0.8794
CarcinogenicityNon-carcinogens0.9329
BiodegradationNot ready biodegradable0.992
Rat acute toxicity2.5624 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9622
hERG inhibition (predictor II)Non-inhibitor0.7246
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, film coatedoral250 mg/1
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point168-171Maeke, S. and Rambacher, P.; US. Patent 4,163,017; July 31,1979; assigned to Diamalt A.G. (Germany).
water solubility89.9 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP4.15SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.0197 mg/mLALOGPS
logP3.01ALOGPS
logP3.71ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)4.6ChemAxon
pKa (Strongest Basic)-0.54ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area77.76 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity109.27 m3·mol-1ChemAxon
Polarizability46.28 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-0a6u-3920000000-ce93b24c6e2568b6087dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)splash10-0a4i-0009000000-82ed6dc62b49ac0340e6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)splash10-01pa-2930000000-64edc819ad56b842cdbaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, N/A (Annotated)splash10-053r-6900000000-c97325e1ca9bcff75af1View in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
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 ReferencesNot Available
External Links
ATC CodesA05AA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (190 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
Aluminum hydroxideThe serum concentration of Chenodeoxycholic acid can be decreased when it is combined with Aluminum hydroxide.
BezafibrateThe therapeutic efficacy of Chenodeoxycholic acid can be decreased when used in combination with Bezafibrate.
CholestyramineThe serum concentration of Chenodeoxycholic acid can be decreased when it is combined with Cholestyramine.
ColesevelamThe serum concentration of Chenodeoxycholic acid can be decreased when it is combined with Colesevelam.
ColestipolThe serum concentration of Chenodeoxycholic acid can be decreased when it is combined with Colestipol.
EstradiolThe therapeutic efficacy of Chenodeoxycholic acid can be decreased when used in combination with Estradiol.
Estrone sulfateThe therapeutic efficacy of Chenodeoxycholic acid can be decreased when used in combination with Estropipate.
FenofibrateThe therapeutic efficacy of Chenodeoxycholic acid can be decreased when used in combination with Fenofibrate.
GemfibrozilThe therapeutic efficacy of Chenodeoxycholic acid can be decreased when used in combination with Gemfibrozil.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt e...
Gene Name:
NR1H4
Uniprot ID:
Q96RI1
Molecular Weight:
55913.915 Da
References
  1. 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. [PubMed:10334992 ]
  2. 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. [PubMed:20104269 ]

Enzymes

Kind
Protein
Organism
Human
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 activity.
Gene Name:
CYP27A1
Uniprot ID:
Q02318
Molecular Weight:
60234.28 Da
References
  1. 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. [PubMed:12385778 ]
  2. Bjorkhem I: Inborn errors of metabolism with consequences for bile acid biosynthesis. A minireview. Scand J Gastroenterol Suppl. 1994;204:68-72. [PubMed:7824882 ]
  3. 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. [PubMed:12011083 ]
  4. Keren Z, Falik-Zaccai TC: Cerebrotendinous xanthomatosis (CTX): a treatable lipid storage disease. Pediatr Endocrinol Rev. 2009 Sep;7(1):6-11. [PubMed:19696711 ]
  5. 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. [PubMed:15576845 ]
  6. 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. [PubMed:12509506 ]
  7. 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. [PubMed:11181760 ]
Kind
Protein
Organism
Human
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. 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. [PubMed:18583509 ]
  2. 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. [PubMed:15454728 ]
Kind
Protein
Organism
Human
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 suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol...
Gene Name:
UGT2B7
Uniprot ID:
P16662
Molecular Weight:
60694.12 Da
References
  1. 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. [PubMed:15821044 ]
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Drug created on September 14, 2010 10:21 / Updated on August 17, 2016 12:24