Tauroursodeoxycholic acid

Identification

Name
Tauroursodeoxycholic acid
Accession Number
DB08834
Type
Small Molecule
Groups
Approved, Investigational
Description

Tauroursodeoxycholic acid is the more hydrophilic form of ursodeoxycholic acid, which is the more abundant naturally produced bile acid in humans. Tauroursodeoxycholic acid, on the other hand, is produced abundantly in bears and has been used for centuries as a natural remedy in some Asian countries. It is approved in Italy and Turkey for the treatment of cholesterol gallstones and is an investigational drug in China, Unites States, and Italy. Tauroursodeoxycholic acid is being investigated for use in several conditions such as Primary Biliary Cirrhosis (PBC), insulin resistance, amyloidosis, Cystic Fibrosis, Cholestasis, and Amyotrophic Lateral Sclerosis. The only completed clinical trial thus far is a phase III clinical trial comparing tauroursodeoxycholic acid and ursofalk in PBC adult patients, but as of June 2013 no results of this trial have been published.

Structure
Thumb
Synonyms
  • Tauroursodeoxycholate
  • Tauroursodesoxycholic acid
  • TUDCA
  • Ursodeoxycholyltaurine
External IDs
UR-906
International/Other Brands
Tauro (Teofarma) / Taurolite (Bio-Gen)
Categories
UNII
60EUX8MN5X
CAS number
14605-22-2
Weight
Average: 499.71
Monoisotopic: 499.296759347
Chemical Formula
C26H45NO6S
InChI Key
BHTRKEVKTKCXOH-LBSADWJPSA-N
InChI
InChI=1S/C26H45NO6S/c1-16(4-7-23(30)27-12-13-34(31,32)33)19-5-6-20-24-21(9-11-26(19,20)3)25(2)10-8-18(28)14-17(25)15-22(24)29/h16-22,24,28-29H,4-15H2,1-3H3,(H,27,30)(H,31,32,33)/t16-,17+,18-,19-,20+,21+,22+,24+,25+,26-/m1/s1
IUPAC Name
2-[(4R)-4-[(1S,2S,5R,7S,9S,10R,11S,14R,15R)-5,9-dihydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-14-yl]pentanamido]ethane-1-sulfonic acid
SMILES

Pharmacology

Indication

Used in the treatment of cholesterol gallstones. Tauroursodeoxycholic acid is also being investigated for use in several conditions such as Primary Biliary Cirrhosis (PBC), insulin resistance, amyloidosis, Cystic Fibrosis, Cholestasis, and Amyotrophic Lateral Sclerosis.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Tauroursodeoxycholic acid is the more hydrophilic form of ursodeoxycholic acid, which is naturally produced in the body. In patients with properly functioning gallbladders, both of these bile acids inhibit liver cholesterol secretion and synthesis as well as intestinal cholesterol absorption allowing for the promotion of cholesterol gallstone dissolution. The mechanism of action of tauroursodeoxycholic acid in the other conditions is still being investigated.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Zhuo, Chao; Feng, Wei; Wu, Da-jun; Xiong, Zhi-gang. Synthesis of tauroursodeoxycholic acid. Hecheng Huaxue (2002), 10(5), 444-446.

General References
  1. Schroeder A, Eckhardt U, Stieger B, Tynes R, Schteingart CD, Hofmann AF, Meier PJ, Hagenbuch B: Substrate specificity of the rat liver Na(+)-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells. Am J Physiol. 1998 Feb;274(2 Pt 1):G370-5. [PubMed:9486191]
  2. Obici L, Cortese A, Lozza A, Lucchetti J, Gobbi M, Palladini G, Perlini S, Saraiva MJ, Merlini G: Doxycycline plus tauroursodeoxycholic acid for transthyretin amyloidosis: a phase II study. Amyloid. 2012 Jun;19 Suppl 1:34-6. doi: 10.3109/13506129.2012.678508. Epub 2012 May 2. [PubMed:22551192]
External Links
KEGG Compound
C16868
PubChem Compound
9848818
PubChem Substance
175427112
ChemSpider
8024531
BindingDB
50236230
ChEBI
80774
ChEMBL
CHEMBL272427
HET
5D5
Drugs.com
Drugs.com Drug Page
Wikipedia
Tauroursodeoxycholic_acid
PDB Entries
5dlv / 5dlw

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentAmyloidosis; Heart (Manifestation) / Senile Cardiac Amyloidosis1
2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS) / Central Nervous System Diseases / Motor Neurone Disease / Nervous System Diseases / Neurodegenerative Disorders / Neuromuscular Diseases / Spinal Cord Diseases / TDP-43 Proteinopathies1
2RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
3CompletedTreatmentCholestatic Liver Disease1
3CompletedTreatmentPrimary Biliary Cirrhosis (PBC)1
4RecruitingPreventionGallstone formation1
Not AvailableCompletedBasic ScienceBMI >30 kg/m2 / Diabetes / Insulin Resistance1
Not AvailableCompletedTreatmentCholestasis1
Not AvailableCompletedTreatmentCystic Fibrosis (CF)1
Not AvailableRecruitingBasic ScienceEndoplasmic Reticulum Stress / HIV Related Insulin Resistance / Protease Inhibitor Related Insulin Resistance1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00748 mg/mLALOGPS
logP1.38ALOGPS
logP1.1ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)-0.8ChemAxon
pKa (Strongest Basic)-0.32ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area123.93 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity130.68 m3·mol-1ChemAxon
Polarizability56.75 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9774
Blood Brain Barrier+0.8416
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.5136
P-glycoprotein inhibitor INon-inhibitor0.6229
P-glycoprotein inhibitor IINon-inhibitor0.7598
Renal organic cation transporterNon-inhibitor0.8476
CYP450 2C9 substrateNon-substrate0.7519
CYP450 2D6 substrateNon-substrate0.7972
CYP450 3A4 substrateSubstrate0.654
CYP450 1A2 substrateNon-inhibitor0.7814
CYP450 2C9 inhibitorNon-inhibitor0.8625
CYP450 2D6 inhibitorNon-inhibitor0.8685
CYP450 2C19 inhibitorNon-inhibitor0.8426
CYP450 3A4 inhibitorNon-inhibitor0.8612
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7175
Ames testNon AMES toxic0.6103
CarcinogenicityNon-carcinogens0.5359
BiodegradationNot ready biodegradable0.972
Rat acute toxicity2.0310 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.706
hERG inhibition (predictor II)Inhibitor0.5549
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as taurinated bile acids and derivatives. These are bile acid derivatives containing a taurine conjugated to the bile acid moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Bile acids, alcohols and derivatives
Direct Parent
Taurinated bile acids and derivatives
Alternative Parents
Dihydroxy bile acids, alcohols and derivatives / 7-alpha-hydroxysteroids / 3-alpha-hydroxysteroids / N-acyl amines / Sulfonyls / Organosulfonic acids / Alkanesulfonic acids / Secondary carboxylic acid amides / Secondary alcohols / Cyclic alcohols and derivatives
show 5 more
Substituents
Taurinated bile acid / Dihydroxy bile acid, alcohol, or derivatives / Hydroxy bile acid, alcohol, or derivatives / 3-hydroxysteroid / Hydroxysteroid / 3-alpha-hydroxysteroid / 7-alpha-hydroxysteroid / 7-hydroxysteroid / Fatty amide / N-acyl-amine
show 22 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
bile acid taurine conjugate (CHEBI:80774) / Taurine conjugates (LMST05040015)

Enzymes

Kind
Protein
Organism
Rat
Pharmacological action
Unknown
Actions
Inducer
General Function
Testosterone 6-beta-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 oxidizes a variety of structurally un...
Gene Name
Cyp3a1
Uniprot ID
P04800
Uniprot Name
Cytochrome P450 3A1
Molecular Weight
57917.375 Da
References
  1. Paolini M, Pozzetti L, Piazza F, Cantelli-Forti G, Roda A: Bile acid structure and selective modulation of murine hepatic cytochrome P450-linked enzymes. Hepatology. 1999 Sep;30(3):730-9. [PubMed:10462380]
Kind
Protein
Organism
Rat
Pharmacological action
Unknown
Actions
Inducer
General Function
Testosterone 6-beta-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 oxidizes a variety of structurally un...
Gene Name
Cyp3a2
Uniprot ID
P05183
Uniprot Name
Cytochrome P450 3A2
Molecular Weight
57731.215 Da
References
  1. Paolini M, Pozzetti L, Piazza F, Cantelli-Forti G, Roda A: Bile acid structure and selective modulation of murine hepatic cytochrome P450-linked enzymes. Hepatology. 1999 Sep;30(3):730-9. [PubMed:10462380]
Kind
Protein
Organism
Rat
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Highly active in the 7-alpha-hydroxylation of testosterone, progesterone and androstenedione.
Gene Name
Cyp2a1
Uniprot ID
P11711
Uniprot Name
Cytochrome P450 2A1
Molecular Weight
55994.635 Da
References
  1. Paolini M, Pozzetti L, Piazza F, Cantelli-Forti G, Roda A: Bile acid structure and selective modulation of murine hepatic cytochrome P450-linked enzymes. Hepatology. 1999 Sep;30(3):730-9. [PubMed:10462380]
Kind
Protein
Organism
Rat
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Highly active in the 15-alpha-hydroxylation of testosterone.
Gene Name
Cyp2a2
Uniprot ID
P15149
Uniprot Name
Cytochrome P450 2A2
Molecular Weight
56344.975 Da
References
  1. Paolini M, Pozzetti L, Piazza F, Cantelli-Forti G, Roda A: Bile acid structure and selective modulation of murine hepatic cytochrome P450-linked enzymes. Hepatology. 1999 Sep;30(3):730-9. [PubMed:10462380]
Kind
Protein
Organism
Rat
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
Cyp2b1
Uniprot ID
P00176
Uniprot Name
Cytochrome P450 2B1
Molecular Weight
55933.06 Da
References
  1. Paolini M, Pozzetti L, Piazza F, Cantelli-Forti G, Roda A: Bile acid structure and selective modulation of murine hepatic cytochrome P450-linked enzymes. Hepatology. 1999 Sep;30(3):730-9. [PubMed:10462380]
Kind
Protein
Organism
Rat
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
Cyp2b2
Uniprot ID
P04167
Uniprot Name
Cytochrome P450 2B2
Molecular Weight
55932.02 Da
References
  1. Paolini M, Pozzetti L, Piazza F, Cantelli-Forti G, Roda A: Bile acid structure and selective modulation of murine hepatic cytochrome P450-linked enzymes. Hepatology. 1999 Sep;30(3):730-9. [PubMed:10462380]
Kind
Protein
Organism
Mouse
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
Cyp2b9
Uniprot ID
P12790
Uniprot Name
Cytochrome P450 2B9
Molecular Weight
55740.36 Da
References
  1. Paolini M, Pozzetti L, Piazza F, Cantelli-Forti G, Roda A: Bile acid structure and selective modulation of murine hepatic cytochrome P450-linked enzymes. Hepatology. 1999 Sep;30(3):730-9. [PubMed:10462380]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. 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:7557095]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Cystine:glutamate antiporter activity
Specific Function
Sodium-independent, high-affinity exchange of anionic amino acids with high specificity for anionic form of cystine and glutamate.
Gene Name
SLC7A11
Uniprot ID
Q9UPY5
Uniprot Name
Cystine/glutamate transporter
Molecular Weight
55422.44 Da
References
  1. Schroeder A, Eckhardt U, Stieger B, Tynes R, Schteingart CD, Hofmann AF, Meier PJ, Hagenbuch B: Substrate specificity of the rat liver Na(+)-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells. Am J Physiol. 1998 Feb;274(2 Pt 1):G370-5. [PubMed:9486191]

Drug created on February 18, 2013 17:42 / Updated on November 09, 2017 04:41