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Identification
Name Ursodeoxycholic acid
Accession Number DB01586
Type small molecule
Groups approved
Description

Ursodeoxycholic acid is an epimer of chenodeoxycholic acid (DB06777). It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • (3alpha,5beta,7beta)-3,7-dihydroxycholan-24-oic acid
  • 3-alpha,7-beta-Dihydroxy-5-beta-cholanoic acid
  • 3-alpha,7-beta-Dihydroxycholanic acid
  • 3-alpha,7-beta-Dioxycholanic acid
  • 3,7-Dihydroxycholan-24-oic acid
  • 3alpha,7beta-Dihydroxy-5beta-cholan-24-oic acid
  • 5beta-Cholan-24-oic acid-3alpha,7beta-diol
  • 7-beta-Hydroxylithocholic acid
  • 7beta-Hydroxylithocholic acid
  • Acide ursodesoxycholique [inn-french]
  • Acido ursodeossicolico [italian]
  • Acido ursodeoxicolico [inn-spanish]
  • Acidum ursodeoxycholicum [inn-latin]
  • Chenodeoxycholic acid
  • Iso-ursodeoxycholic acid
  • UDCS
  • Ursodesoxycholic acid
  • Ursodiol
Brand names
  • Actigall
  • Antigall
  • Arsacol
  • Cholit-ursan
  • Delursan
  • Destolit
  • Deursil
  • Dom-ursodiol c
  • Litursol
  • Lyeton
  • Peptarom
  • PHL-ursodiol c
  • PMS-ursodiol c
  • Solutrat
  • Ursacol
  • Urso
  • Urso 250
  • Urso DS
  • Urso forte
  • Ursobilin
  • Ursochol
  • Ursodamor
  • Ursofalk
  • Ursolvan
Brand name mixtures Not Available
Categories
  • Cholagogues and Choleretics
CAS number 128-13-2
Weight Average: 392.572
Monoisotopic: 392.292659768
Chemical Formula C24H40O4
InChI Key InChIKey=RUDATBOHQWOJDD-UZVSRGJWSA-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
Plain Text
IUPAC Name
(4R)-4-[(1S,2S,5R,7S,9S,10R,11S,14R,15R)-5,9-dihydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Bile Acids
Substructures
  • Bile Acids
  • Steroids and Steroid Derivatives
  • Hydroxy Compounds
  • Acetates
  • Sterols
  • Carboxylic Acids and Derivatives
  • Bicyclohexanes
  • Alcohols and Polyols
Pharmacology
Indication The drug reduces cholesterol absorption and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery.
Pharmacodynamics Ursodiol (also known as ursodeoxycholic acid) is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. Primary bile acids are produced by the liver and stored in the gall bladder. When secreted into the colon, primary bile acids can be metabolized into secondary bile acids by intestinal bacteria. Primary and secondary bile acids help the body digest fats. Ursodeoxycholic acid helps regulate cholesterol by reducing the rate at which the intestine absorbs cholesterol molecules while breaking up micelles containing cholesterol. Because of this property, ursodeoxycholic acid is used to treat gall stones non-surgically.
Mechanism of action Ursodeoxycholic acid reduces elevated liver enzyme levels by facilitating bile flow through the liver and protecting liver cells. The main mechanism if anticholelithic. Although the exact process of ursodiol's anticholelithic action is not completely understood, it is thought that the drug is concentrated in bile and decreases biliary cholesterol by suppressing hepatic synthesis and secretion of cholesterol and by inhibiting its intestinal absorption. The reduced cholesterol saturation permits the gradual solubilization of cholesterol from gallstones, resulting in their eventual dissolution.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Route of elimination Only small quantities of ursodiol appear in the systemic circulation and very small amounts are excreted into urine. Eighty percent of lithocholic acid formed in the small bowel is excreted in the feces, but the 20% that is absorbed is sulfated at the 3-hydroxyl group in the liver to relatively insoluble lithocholyl conjugates which are excreted into bile and lost in feces.
Half life Not Available
Clearance Not Available
Toxicity Neither accidental nor intentional overdosing with ursodeoxycholic acid has been reported. Doses of ursodeoxycholic acid in the range of 16-20 mg/kg/day have been tolerated for 6-37 months without symptoms by 7 patients. The LD50 for ursodeoxycholic acid in rats is over 5000 mg/kg given over 7-10 days and over 7500 mg/kg for mice. The most likely manifestation of severe overdose with ursodeoxycholic acid would probably be diarrhea, which should be treated symptomatically.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Watson pharmaceuticals inc
  • Corepharma llc
  • Epic pharma llc
  • Lannett holdings inc
  • Mylan pharmaceuticals inc
  • Teva pharmaceuticals usa
  • Axcan pharma us inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Urso forte 500 mg tablet 6.3 USD tablet
Actigall 300 mg capsule 5.52 USD capsule
Ursodiol 500 mg tablet 4.75 USD tablet
Urso 250 mg tablet 4.41 USD tablet
Urso 250 250 mg tablet 3.55 USD tablet
Urso Ds 500 mg Tablet 2.69 USD tablet
Ursodiol 250 mg tablet 2.68 USD tablet
Pms-Ursodiol C 500 mg Tablet 1.75 USD tablet
Urso 250 mg Tablet 1.42 USD tablet
Pms-Ursodiol C 250 mg Tablet 0.92 USD tablet
Patents Not Available
Properties
State solid
Melting point 203 oC
Experimental Properties
Property Value Source
water solubility 0.02 mg/mL at 20 oC [YALKOWSKY,SH & DANNENFELSER,RM (1992)] PhysProp
logP 3.00 [RODA,A ET AL. (1990)] PhysProp
Predicted Properties
Property Value Source
water solubility 1.97e-02 g/l ALOGPS
logP 3.01 ALOGPS
logP 3.71 ChemAxon Molconvert
logS -4.30 ALOGPS
pKa 18.30 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 77.76 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 109.27 ChemAxon Molconvert
polarizability 46.33 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Akare S, Jean-Louis S, Chen W, Wood DJ, Powell AA, Martinez JD: Ursodeoxycholic acid modulates histone acetylation and induces differentiation and senescence. Int J Cancer. 2006 Dec 15;119(12):2958-69. Pubmed
  2. Smith T, Befeler AS: High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Curr Gastroenterol Rep. 2007 Mar;9(1):54-9. Pubmed
  3. Jackson H, Solaymani-Dodaran M, Card TR, Aithal GP, Logan R, West J: Influence of ursodeoxycholic acid on the mortality and malignancy associated with primary biliary cirrhosis: A population-based cohort study. Hepatology. 2007 Aug 8;46(4):1131-1137. Pubmed
External Links
Resource Link
KEGG Drug D00734 Link_out
KEGG Compound C07880 Link_out
PubChem Compound 31401 Link_out
PubChem Substance 46508795 Link_out
ChemSpider 29131 Link_out
ChEBI 9907 Link_out
ChEMBL 9907 Link_out
Therapeutic Targets Database DNC000420 Link_out
HET IU5 Link_out
Drug Product Database 2238984 Link_out
Wikipedia http://en.wikipedia.org/wiki/Ursodiol Link_out
ATC Codes
  • A05AA02
AHFS Codes
  • 56:14.00
PDB Entries
FDA label show (233 KB)
MSDS show (73.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Aldo-keto reductase family 1 member C2

Pharmacological action: yes
Actions: inducer

Works in concert with the 5alpha/5beta-steroid reductases to convert steroid hormones into the 3alpha/5alpha and 3alpha/5beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5alpha-DHT) to 5-alpha-androstane-3alpha,17beta-diol (3-alpha-diol)

Organism class: human
UniProt ID: P52895 Link_out
Gene: AKR1C2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Amaral JD, Sola S, Steer CJ, Rodrigues CM: Role of nuclear steroid receptors in apoptosis. Curr Med Chem. 2009;16(29):3886-902. Pubmed
Enzymes

1. Cytochrome P450 2E1

Actions: inhibitor, inducer

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Bile salt export pump

Actions: substrate, inhibitor, inducer

Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes

UniProt ID: O95342 Link_out
Gene: ABCB11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Schuetz EG, Strom S, Yasuda K, Lecureur V, Assem M, Brimer C, Lamba J, Kim RB, Ramachandran V, Komoroski BJ, Venkataramanan R, Cai H, Sinal CJ, Gonzalez FJ, Schuetz JD: Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450. J Biol Chem. 2001 Oct 19;276(42):39411-8. Epub 2001 Aug 16. Pubmed
  2. Green RM, Hoda F, Ward KL: Molecular cloning and characterization of the murine bile salt export pump. Gene. 2000 Jan 4;241(1):117-23. Pubmed
  3. Mita S, Suzuki H, Akita H, Stieger B, Meier PJ, Hofmann AF, Sugiyama Y: Vectorial transport of bile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump. Am J Physiol Gastrointest Liver Physiol. 2005 Jan;288(1):G159-67. Epub 2004 Aug 5. Pubmed

2. Solute carrier organic anion transporter family member 1A2

Actions: substrate, inhibitor, inducer

Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity)

UniProt ID: P46721 Link_out
Gene: SLCO1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Fickert P, Zollner G, Fuchsbichler A, Stumptner C, Pojer C, Zenz R, Lammert F, Stieger B, Meier PJ, Zatloukal K, Denk H, Trauner M: Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. Gastroenterology. 2001 Jul;121(1):170-83. Pubmed
  2. Kullak-Ublick GA, Hagenbuch B, Stieger B, Schteingart CD, Hofmann AF, Wolkoff AW, Meier PJ: Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology. 1995 Oct;109(4):1274-82. Pubmed
  3. Kullak-Ublick GA, Hagenbuch B, Stieger B, Wolkoff AW, Meier PJ: Functional characterization of the basolateral rat liver organic anion transporting polypeptide. Hepatology. 1994 Aug;20(2):411-6. Pubmed
  4. Hata S, Wang P, Eftychiou N, Ananthanarayanan M, Batta A, Salen G, Pang KS, Wolkoff AW: Substrate specificities of rat oatp1 and ntcp: implications for hepatic organic anion uptake. Am J Physiol Gastrointest Liver Physiol. 2003 Nov;285(5):G829-39. Epub 2003 Jul 3. Pubmed

3. Canalicular multispecific organic anion transporter 1

Actions: inducer

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM, Edwards PA: Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem. 2002 Jan 25;277(4):2908-15. Epub 2001 Nov 12. Pubmed
  2. Fickert P, Zollner G, Fuchsbichler A, Stumptner C, Pojer C, Zenz R, Lammert F, Stieger B, Meier PJ, Zatloukal K, Denk H, Trauner M: Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. Gastroenterology. 2001 Jul;121(1):170-83. Pubmed

4. Multidrug resistance-associated protein 4

Actions: inhibitor

May be an organic anion pump relevant to cellular detoxification

UniProt ID: O15439 Link_out
Gene: ABCC4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Rius M, Nies AT, Hummel-Eisenbeiss J, Jedlitschky G, Keppler D: Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology. 2003 Aug;38(2):374-84. Pubmed

5. Ileal sodium/bile acid cotransporter

Actions: inhibitor

Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism

UniProt ID: Q12908 Link_out
Gene: SLC10A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Craddock AL, Love MW, Daniel RW, Kirby LC, Walters HC, Wong MH, Dawson PA: Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol. 1998 Jan;274(1 Pt 1):G157-69. Pubmed
  2. Saeki T, Matoba K, Furukawa H, Kirifuji K, Kanamoto R, Iwami K: Characterization, cDNA cloning, and functional expression of mouse ileal sodium-dependent bile acid transporter. J Biochem. 1999 Apr;125(4):846-51. Pubmed
  3. Saeki T, Takahashi N, Kanamoto R, Iwami K: Characterization of cloned mouse Na+/taurocholate cotransporting polypeptide by transient expression in COS-7 cells. Biosci Biotechnol Biochem. 2002 May;66(5):1116-8. Pubmed

6. Sodium/bile acid cotransporter

Actions: substrate, inhibitor

The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presence of sodium

UniProt ID: Q14973 Link_out
Gene: SLC10A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Boyer JL, Ng OC, Ananthanarayanan M, Hofmann AF, Schteingart CD, Hagenbuch B, Stieger B, Meier PJ: Expression and characterization of a functional rat liver Na+ bile acid cotransport system in COS-7 cells. Am J Physiol. 1994 Mar;266(3 Pt 1):G382-7. Pubmed
  2. Mita S, Suzuki H, Akita H, Stieger B, Meier PJ, Hofmann AF, Sugiyama Y: Vectorial transport of bile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump. Am J Physiol Gastrointest Liver Physiol. 2005 Jan;288(1):G159-67. Epub 2004 Aug 5. Pubmed
Comments
Drug created on August 29, 2007 08:57 / Updated on November 10, 2010 13:49

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.