Identification
NameTauroursodeoxycholic acid
Accession NumberDB08834
TypeSmall Molecule
GroupsApproved, 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
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TauroTeofarma
TauroliteBio-Gen
Brand mixturesNot Available
Categories
UNII60EUX8MN5X
CAS number14605-22-2
WeightAverage: 499.71
Monoisotopic: 499.296759347
Chemical FormulaC26H45NO6S
InChI KeyBHTRKEVKTKCXOH-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
[H][C@@]12CC[[email protected]]([[email protected]](C)CCC(=O)NCCS(O)(=O)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])[C@@H](O)C[C@]2([H])C[[email protected]](O)CC[C@]12C
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
PharmacodynamicsNot 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.

Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot 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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2Active Not RecruitingTreatmentAmyloidosis; 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
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassBile acids, alcohols and derivatives
Direct ParentTaurinated bile acids and derivatives
Alternative ParentsDihydroxy 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
SubstituentsTaurinated 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 acyl / Fatty amide
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptorsbile 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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
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 inhibited by the grapefruit juice component naringin.
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 June 11, 2017 21:21