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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H40O4
Molecular Weight 392.5729
Optical Activity UNSPECIFIED
Defined Stereocenters 10 / 10
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CHENODIOL

SMILES

C[C@]([H])(CCC(=O)O)[C@@]1([H])CC[C@@]2([H])[C@@]3([H])[C@]([H])(CC[C@]12C)[C@@]4(C)CC[C@]([H])(C[C@@]4([H])C[C@@]3([H])O)O

InChI

InChIKey=RUDATBOHQWOJDD-BSWAIDMHSA-N
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

HIDE SMILES / InChI

Molecular Formula C24H40O4
Molecular Weight 392.5729
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 10 / 10
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB01586

Ursodiol tablets, USP are bile acids indicated for the treatment of patients with primary biliary cirrhosis. Ursodiol (Ursodeoxycholic acid), a naturally occurring hydrophilic bile acid, derived from cholesterol, is present as a minor fraction of the total human bile acid pool. 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. In addition to the replacement and displacement of toxic bile acids, other mechanisms of action include cytoprotection of the injured bile duct epithelial cells (cholangiocytes) against toxic effects of bile acids, inhibition of apotosis of hepatocytes, immunomodulatory effects, and stimulation of bile secretion by hepatocytes and cholangiocytes. 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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Chenodiol

Approved Use

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. The likelihood of successful dissolution is far greater if the stones are floatable or small. For patients with nonfloatable stones, dissolution is less likely and added weight should be given to the risk that more emergent surgery might result form a delay due to unsuccessful treatment.

Launch Date

4.28198396E11
Primary
URSODIOL

Approved Use

Ursodiol

Launch Date

6.1655037E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
15.2 μM
15 mg/kg bw 1 times / day multiple, oral
dose: 15 mg/kg bw
route of administration: Oral
experiment type: MULTIPLE
co-administered:
URSODIOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
49.8 μM × h
15 mg/kg bw 1 times / day multiple, oral
dose: 15 mg/kg bw
route of administration: Oral
experiment type: MULTIPLE
co-administered:
URSODIOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
50 mg/kg 3 times / day multiple, oral (total daily dose)
Highest studied dose
Dose: 50 mg/kg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg/kg, 3 times / day
Sources: Page: p.18
unhealthy, 37-65
n = 7
Health Status: unhealthy
Condition: Amyotrophic lateral sclerosis
Age Group: 37-65
Sex: M+F
Population Size: 7
Sources: Page: p.18
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources: Page: p.4
unhealthy
n = 60
Health Status: unhealthy
Condition: Primary biliary cirrhosis
Population Size: 60
Sources: Page: p.4
Disc. AE: Nausea...
AEs leading to
discontinuation/dose reduction:
Nausea (1.7%)
Sources: Page: p.4
AEs

AEs

AESignificanceDosePopulation
Nausea 1.7%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources: Page: p.4
unhealthy
n = 60
Health Status: unhealthy
Condition: Primary biliary cirrhosis
Population Size: 60
Sources: Page: p.4
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [Inhibition 20 uM]
yes
no (co-administration study)
Comment: UDCA did not lead to detectable changes in midazolam pharmacokinetics
yes
weak (co-administration study)
Comment: UDCA modestly decreased digoxin disposition without
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Toxicity of chenodeoxycholic acid in the rhesus monkey.
1975 Aug
Medical treatment of gallstones.
1975 Jan
Toxicity of chenodeoxycholic acid in the nonhuman primate.
1975 Jun
Effects of clofibrate in primary biliary cirrhosis hypercholesterolemia and gallstones.
1975 Oct
Extracorporeal shock wave lithotripsy of gallstones with oral dissolution. Results in course of ten years in Czech Republic in correlation to indication criteria.
2001
Suppression of renal disease and mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE) by chenodeoxycholic acid.
2001
Enzyme immunoassay for conjugated 7alpha-hydroxy-3-oxo-4-cholenoic acid in human urine.
2001
Cerebrotendinous xanthomatosis.
2001 Aug
Effect of bile acids on formation of azoxymethane-induced aberrant crypt foci in colostomized F344 rat colon.
2001 Aug 28
Anti-inflammatory effects of 5-aminosalicylic acid conjugates with chenodeoxycholic acid and ursodeoxycholic acid on carrageenan-induced colitis in guinea-pigs.
2001 Dec
Effect of bile acids on absorption of nitrendipine in healthy subjects.
2001 Dec
Duodenal reflux induces cyclooxygenase-2 in the esophageal mucosa of rats: evidence for involvement of bile acids.
2001 Dec
Antagonism of the actions of peroxisome proliferator-activated receptor-alpha by bile acids.
2001 Dec 14
Enhanced expression of the human multidrug resistance protein 3 by bile salt in human enterocytes. A transcriptional control of a plausible bile acid transporter.
2001 Dec 14
Chenodeoxycholate is a potent inducer of the permeability transition pore in rat liver mitochondria.
2001 Feb
Cerebrotendinous xanthomatosis presenting as "chologenic diarrhoea".
2001 Jul
Effect of bile salts on colonic mucus secretion in isolated vascularly perfused rat colon.
2001 Jun
Enhancement of endothelial nitric oxide production by chenodeoxycholic acids in patients with hepatobiliary diseases.
2001 May
Synthetic bile acid derivatives induce nonapoptotic death of human retinal pigment epithelial cells.
2001 May
Reduced activity of 11 beta-hydroxysteroid dehydrogenase in patients with cholestasis.
2001 Nov
3beta-hydroxy-delta5 -C27-steroid dehydrogenase deficiency: diagnosis and treatment.
2001 Oct
Acute effects of dietary fat composition on postprandial plasma bile acid and cholecystokinin concentrations in healthy premenopausal women.
2001 Oct
Farnesoid X-activated receptor induces apolipoprotein C-II transcription: a molecular mechanism linking plasma triglyceride levels to bile acids.
2001 Oct
Effects of bile acids on the humoral immune response: a mechanistic approach.
2001 Oct 5
External biliary drainage plus bile acid feeding is not equal to internal drainage in preserving the cellular immunity following prolonged obstructive jaundice.
2001 Sep
Biliary excretion of tauroursodeoxycholate-3-sulfate in the rat.
2001 Sep
Nuclear receptor-mediated repression of human cholesterol 7alpha-hydroxylase gene transcription by bile acids.
2001 Sep
[Cerebrotendinous xanthomatosis].
2001 Sep 1
Cerebrotendinous xanthomatosis: 11-year treatment with chenodeoxycholic acid in five patients. An electrophysiological study.
2001 Sep 15
Cerebrotendinous xanthomatosis: a rare disease with diverse manifestations.
2002 Apr
Inhibition of the MAPK and PI3K pathways enhances UDCA-induced apoptosis in primary rodent hepatocytes.
2002 Apr
Conversion of 7 alpha-hydroxycholesterol to bile acid in human subjects: is there an alternate pathway favoring cholic acid synthesis?
2002 Feb
Guest-responsive fluorescence variations of gamma-cyclodextrins labeled with hetero-functionalized pyrene and tosyl moieties.
2002 Feb
MALDI-TOF-MS analysis of droplets prepared in an electrodynamic balance: "wall-less" sample preparation.
2002 Feb 1
Interactions of combined bile acids on hepatocyte viability: cytoprotection or synergism.
2002 Feb 7
Demonstration of a direct stimulatory effect of bile salts on rat colonic epithelial cell proliferation.
2002 Jan
Chenodeoxycholic acid and deoxycholic acid inhibit 11 beta-hydroxysteroid dehydrogenase type 2 and cause cortisol-induced transcriptional activation of the mineralocorticoid receptor.
2002 Jul 19
The amino acid residues asparagine 354 and isoleucine 372 of human farnesoid X receptor confer the receptor with high sensitivity to chenodeoxycholate.
2002 Jul 19
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.
2002 Jul 26
Participation of two members of the very long-chain acyl-CoA synthetase family in bile acid synthesis and recycling.
2002 Jul 5
Two novel mutations in the sterol 27-hydroxylase gene causing cerebrotendinous xanthomatosis.
2002 Mar
The UDCA dosage deficit: a fate shared with CDCA.
2002 Mar
Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump.
2002 Mar
Unconjugated bile acids modulate adult and neonatal neutrophil chemotaxis induced in vitro by N-formyl-met-leu-phe-peptide.
2002 Mar
Characterization of rat liver bile acid acyl glucuronosyltransferase.
2002 Mar
The proximal colonic motor response to rectal mechanical and chemical stimulation.
2002 Mar
[Treatment of cholestatic liver diseases].
2002 Mar 15
Relationship between asymptomatic hypercholanaemia of pregnancy and progesterone metabolism.
2002 May
A novel primary bile acid in the Shoebill stork and herons and its phylogenetic significance.
2002 May
A natural product that lowers cholesterol as an antagonist ligand for FXR.
2002 May 31
Patents

Sample Use Guides

In Vivo Use Guide
The recommended dose range for Chenodiol is 13 to 16 mg/kg/day in two divided doses, morning and night, starting with 250 mg b.i.d. the first two weeks and increasing by 250 mg/day each week thereafter until the recommended or maximum tolerated dose is reached. If diarrhea occurs during dosage buildup or later in treatment, it usually can be controlled by temporary dosage adjustment until symptoms abate, after which the previous dosage usually is tolerated. Dosage less than 10 mg/kg usually is ineffective and may be associated with increased risk of cholecystectomy, so is not recommended.
Route of Administration: Oral
Hepatocytes were treated with Chenodiol at 10, 30, and 100 uM for 48 h, and RNA was extracted for real-time PCR analysis. Chenodiol markedly suppressed CYP7A1, the rate-limiting enzyme of bile acid synthesis, but only moderately (35%) down-regulated CYP8B1 at a high concentration of 100uM. Chenodiol increased the two major target genes of the farnesoid X receptor (FXR), namely the small heterodimer partner (SHP) by fourfold, and markedly induced fibroblast growth factor 19 (FGF19) over 100-fold.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:14:25 UTC 2021
Edited
by admin
on Fri Jun 25 21:14:25 UTC 2021
Record UNII
0GEI24LG0J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CHENODIOL
MI   ORANGE BOOK   USAN   VANDF  
USAN  
Official Name English
3.ALPHA.,7.ALPHA.-DIHYDROXY-5.BETA.-CHOLAN-24-OIC ACID
Systematic Name English
CHENODEOXYCHOLIC ACID
EP   INN   MART.   VANDF   WHO-DD  
INN  
Official Name English
CHENODEOXYCHOLIC ACID [EP MONOGRAPH]
Common Name English
NSC-657949
Code English
CHENODEOXYCHOLIC ACID [MART.]
Common Name English
CHENODIOL [MI]
Common Name English
CHENODEOXYCHOLATE
Common Name English
CHENODIOL [USAN]
Common Name English
NSC-757798
Code English
ANTHROPODESOXYCHOLIC ACID
Common Name English
CHENODEOXYCHOLIC ACID [EP]
Common Name English
CHENODIOL [VANDF]
Common Name English
CHOLANORM
Brand Name English
CHENODEOXYCHOLIC ACID [INN]
Common Name English
CHENOFALK
Brand Name English
CHENIX
Brand Name English
CHENOCOL
Brand Name English
CHENODIOL [ORANGE BOOK]
Common Name English
CHOLAN-24-OIC ACID, 3,7-DIHYDROXY-, (3.ALPHA.,5.BETA.,7.ALPHA.)
Common Name English
CHENODEOXYCHOLIC ACID [JAN]
Common Name English
CHENDOL
Brand Name English
GALLODESOXYCHOLIC ACID
Common Name English
FLUIBIL
Brand Name English
CHENOSSIL
Brand Name English
URSODEOXYCHOLIC ACID IMPURITY A [EP]
Common Name English
CHENODESOXYCHOLIC ACID
Common Name English
CHENIC ACID
Common Name English
ANTHROPODODESOXYCHOLIC ACID
Common Name English
ANTHROPODEOXYCHOLIC ACID
Common Name English
CHENODEOXYCHOLIC ACID [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 300510
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
LOINC 30519-3
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
NCI_THESAURUS C66913
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
EU-Orphan Drug EU/3/14/1406
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
FDA ORPHAN DRUG 175303
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
LOINC 2065-1
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
FDA ORPHAN DRUG 3384
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
LIVERTOX 186
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
FDA ORPHAN DRUG 235406
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
WHO-ATC A05AA01
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
WHO-VATC QA05AA01
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
Code System Code Type Description
CAS
474-25-9
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
FDA UNII
0GEI24LG0J
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
IUPHAR
608
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
PUBCHEM
10133
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
DRUG CENTRAL
4361
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
WIKIPEDIA
CHENODEOXYCHOLIC ACID
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
DRUG BANK
DB06777
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
ChEMBL
CHEMBL240597
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
MERCK INDEX
M3324
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY Merck Index
RXCUI
42588
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
ALTERNATIVE
MESH
D002635
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
INN
4391
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
EPA CompTox
474-25-9
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
EVMPD
SUB07463MIG
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
NCI_THESAURUS
C65206
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
ECHA (EC/EINECS)
207-481-8
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
RXCUI
2323
Created by admin on Fri Jun 25 21:14:25 UTC 2021 , Edited by admin on Fri Jun 25 21:14:25 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TRANSPORTER -> INHIBITOR
TARGET -> AGONIST
CDCA, had a half-maximal effective concentration (EC50) of 50 mMand 10 micromolar murine and human FXR, respectively (Fig. 1B). These concentrations are well within the physiologic intracellular range reported in vivo (11).
AGONIST
IC50
METABOLIC ENZYME -> SUBSTRATE
MINOR
SALT/SOLVATE -> PARENT
TARGET -> AGONIST
TRANSPORTER -> INHIBITOR
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IN VITRO
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METABOLITE -> PARENT
IN VITRO
MINOR
PARENT -> METABOLITE
BILE
METABOLITE -> PARENT
IN VITRO
MAJOR
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PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC