CHOLIC ACID

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H40O5
Molecular Weight	408.5714
Optical Activity	UNSPECIFIED
Defined Stereocenters	11 / 11
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

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])C[C@H](O)[C@]12C)[C@H](C)CCC(O)=O

InChI

InChIKey=BHQCQFFYRZLCQQ-OELDTZBJSA-N

InChI=1S/C24H40O5/c1-13(4-7-21(28)29)16-5-6-17-22-18(12-20(27)24(16,17)3)23(2)9-8-15(25)10-14(23)11-19(22)26/h13-20,22,25-27H,4-12H2,1-3H3,(H,28,29)/t13-,14+,15-,16-,17+,18+,19-,20+,22+,23+,24-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C24H40O5
Molecular Weight	408.5714
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	10 / 11
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205750s000lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm438572.htm

Cholic acid is a primary bile acid synthesized from cholesterol in the liver. Endogenous bile acids including cholic acid enhance bile flow and provide the physiologic feedback inhibition of bile acid synthesis. The mechanism of action of cholic acid has not been fully established; however, it is known that cholic acid and its conjugates are endogenous ligands of the nuclear receptor, farnesoid X receptor (FXR). FXR regulates enzymes and transporters that are involved in bile acid synthesis and in the enterohepatic circulation to maintain bile acid homeostasis under normal physiologic conditions. U.S. Food and Drug Administration approved Cholbam (cholic acid) capsules, the first FDA approved treatment for pediatric and adult patients with bile acid synthesis disorders due to single enzyme defects, and for patients with peroxisomal disorders (including Zellweger spectrum disorders).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bile acid receptor FXR 31 Target ID: CHEMBL2047 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25073467 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205750s000lbl.pdf	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Bile acid synthesis disorders 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205750s000lbl.pdf	Primary		Approved 8429	CHOLBAM Approved Use CHOLBAM® (cholic acid) is a bile acid indicated for the treatment of Bile Acid Synthesis Disorders due to single enzyme defects (SEDs) and Adjunctive treatment of peroxisomal disorders (PDs) including Zellweger Spectrum Disorders in patients who exhibit manifestations of liver disease, steatorrhea or complications from decreased fat soluble vitamin absorption Launch Date 2015
Peroxisomal disorders 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205750s000lbl.pdf	Primary		Approved 8429	CHOLBAM Approved Use CHOLBAM® (cholic acid) is a bile acid indicated for the treatment of Bile Acid Synthesis Disorders due to single enzyme defects (SEDs) and Adjunctive treatment of peroxisomal disorders (PDs) including Zellweger Spectrum Disorders in patients who exhibit manifestations of liver disease, steatorrhea or complications from decreased fat soluble vitamin absorption Launch Date 2015

Doses

Dose	Population	Adverse events
10 mg/kg 1 times / day multiple, oral Recommended Dose: 10 mg/kg, 1 times / day Route: oral Route: multiple Dose: 10 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205750lbl.pdf	unhealthy, 19 - 36 years n = 31 Health Status: unhealthy Condition: single enzyme defects Age Group: 19 - 36 years Sex: M+F Population Size: 31 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205750lbl.pdf	Disc. AE: Peripheral neuropathy... AEs leading to discontinuation/dose reduction: Peripheral neuropathy (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205750lbl.pdf
61.5 mg/kg 1 times / day multiple, oral Highest studied dose Dose: 61.5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 61.5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205750Orig1s000MedR.pdf Page: p. 58	unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205750Orig1s000MedR.pdf Page: p. 58	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205750Orig1s000MedR.pdf Page: p. 58

AEs

AE	Significance	Dose	Population
Peripheral neuropathy	1 patient Disc. AE	10 mg/kg 1 times / day multiple, oral Recommended Dose: 10 mg/kg, 1 times / day Route: oral Route: multiple Dose: 10 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205750lbl.pdf	unhealthy, 19 - 36 years n = 31 Health Status: unhealthy Condition: single enzyme defects Age Group: 19 - 36 years Sex: M+F Population Size: 31 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205750lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	BSEP 52 ASBT 3

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
ASBT 3	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205750Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	yes
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205750Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:16359	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:16359
ChemicalBook	CB52741764	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB52741764
ChemicalBook	CB9263222	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9263222
MolPort	MolPort-003-892-613	https://www.molport.com/shop/molecule-link/MolPort-003-892-613
ZINC	ZINC000006858022	http://zinc15.docking.org/substances/ZINC000006858022
eMolecules	29504030	https://www.emolecules.com/cgi-bin/more?vid=29504030
eMolecules	29541145	https://www.emolecules.com/cgi-bin/more?vid=29541145
eMolecules	30512922	https://www.emolecules.com/cgi-bin/more?vid=30512922

PubMed

Title	Date	PubMed
Differential modulation of cellular death and survival pathways by conjugated bile acids.	2001	11707155
Influence of plasma triglyceride and plasma cholesterol levels on the clearance rate of fibrinogen.	2001	11460525
Characterization, stability and in-vivo distribution of asialofetuin glycopeptide incorporating DSPC/CHOL liposomes prepared by mild cholate incubation.	2001 Apr	11697109
Design and properties of hepatitis C virus antisense oligonucleotides for liver specific drug targeting.	2001 Apr-Jul	11563018
On-line identification of trans- and cis-resveratrol by nonaqueous capillary electrophoresis/fluorescence spectroscopy at 77 K.	2001 Aug	11519961
A double antibody sandwich enzyme-linked immunosorbent assay for the detection of Salmonella using biotinylated monoclonal antibodies.	2001 Aug	11510654
1H- and (31)P-MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy-characteristic profiles of water soluble and lipophilic spectral components.	2001 Aug	11477651
Non-obese diabetic (NOD) mice exhibit an increased cellular immune response to glycated-LDL but are resistant to high fat diet induced atherosclerosis.	2001 Aug	11472727
Effect of bile acids on formation of azoxymethane-induced aberrant crypt foci in colostomized F344 rat colon.	2001 Aug 28	11431100
Rim1 and rabphilin-3 bind Rab3-GTP by composite determinants partially related through N-terminal alpha -helix motifs.	2001 Aug 31	11431472
Ion conductors derived from cholic acid and spermine: importance of facial hydrophilicity on NA(+) transport and membrane selectivity.	2001 Aug 8	11480993
Bile acid metabolism by fresh human colonic contents: a comparison of caecal versus faecal samples.	2001 Dec	11709519
Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate: a prospective, randomised, double blind, placebo controlled trial.	2001 Dec	11709518
Dietary cholate increases plasma levels of apolipoprotein B in mice by posttranscriptional mechanisms.	2001 Dec	11606258
Antagonism of the actions of peroxisome proliferator-activated receptor-alpha by bile acids.	2001 Dec 14	11606578
Cross-Linking study of cytochrome P450 1A2 in proteoliposomes.	2001 Feb	11508695
Metabolic and functional properties of lactic acid bacteria in the gastro-intestinal ecosystem: a comparative in vitro study between bacteria of intestinal and fermented food origin.	2001 Jul	11518324
Stacking and separation of coproporphyrin isomers by acetonitrile-salt mixtures in micellar electrokinetic chromatography.	2001 Jul	11504047
Fetal bile acid metabolism: analysis of urinary 3beta-monohydroxy-delta(5) bile acid in preterm infants.	2001 Jul	11474144
Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver.	2001 Jul	11438506
Synthesis and properties of bile acid phosphoramidites 5'-tethered to antisense oligodeoxynucleotides against HCV.	2001 Jul	11425584
Influence of natural, electrically neutral lipids on the potentiometric responses of cation-selective polymeric membrane electrodes.	2001 Jul 15	11476216
Separation and selectivity of benzophenones in micellar electrokinetic chromatography using sodium dodecyl sulfate micelles or sodium cholate modified mixed micelles.	2001 Jul 20	11510546
Analysis of post-harvest fungicides by micellar electrokinetic chromatography.	2001 Jul 27	11521888
Transmembrane ion channels constructed of cholic acid derivatives.	2001 Jul 27	11463261
Monitored selection of DNA-hybrids forming duplexes with capped terminal C:G base pairs.	2001 Jul-Aug	11442395
Effect of bile salts on colonic mucus secretion in isolated vascularly perfused rat colon.	2001 Jun	11414298
Surfactant, but not the size of solid lipid nanoparticles (SLN) influences viability and cytokine production of macrophages.	2001 Jun 19	11397567
Enhancement of endothelial nitric oxide production by chenodeoxycholic acids in patients with hepatobiliary diseases.	2001 May	11605772
Controlled expansion of a molecular cavity in a steroid host compound.	2001 May 16	11457222
[Dietary cholesterol modifies pyroglutamyl aminopeptidase activity in mouse frontal cortex. Sexual differences].	2001 May 16-31	11424043
A truncation of 2B subfamily cytochromes P450 yields increased expression levels, increased solubility, and decreased aggregation while retaining function.	2001 Nov 1	11673866
Circular dichroism spectra of the achiral guest N-aryl-N-nitrosamines included in the crystal host matrices of cholic acid.	2001 Nov 2	11681951
Efficient gene delivery via non-covalent complexes of folic acid and polyethylenimine.	2001 Nov 9	11689266
Transcriptional regulation of the human sterol 12alpha-hydroxylase gene (CYP8B1): roles of heaptocyte nuclear factor 4alpha in mediating bile acid repression.	2001 Nov 9	11535594
Human liver UDP-glucuronosyltransferase isoforms involved in the glucuronidation of 7-ethyl-10-hydroxycamptothecin.	2001 Oct	11695848
In vitro excystation of Paragonimus heterotremus metacercariae.	2001 Oct	11695393
Pericentral hepatocytes translocate hydrophilic bile acids more rapidly than hydrophobic ones.	2001 Oct	11680582
Colonic transit influences deoxycholic acid kinetics.	2001 Oct	11606495
Farnesoid X-activated receptor induces apolipoprotein C-II transcription: a molecular mechanism linking plasma triglyceride levels to bile acids.	2001 Oct	11579204
Evidence for an umbrella mechanism of bilayer transport.	2001 Oct 10	11583569
NMR diffusion spectroscopy as a measure of host-guest complex association constants and as a probe of complex size.	2001 Oct 19	11597206
Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450.	2001 Oct 19	11509573
Potency of select statin drugs in a new mouse model of hyperlipidemia and atherosclerosis.	2001 Oct 23	11604260
Simultaneous detection of cholyl adenylate and coenzyme A thioester utilizing liquid chromatography/electrospray ionization mass spectrometry.	2001 Sep	11708055
Effect of different bile salts on the relative hypoglycemia of witepsol W35 suppositories containing insulin in diabetic Beagle dogs.	2001 Sep	11699836
Evaluation of polymeric nanoparticles composed of cholic acid and methoxy poly(ethylene glycol).	2001 Sep 11	11532566
Side chain hydroxylations in bile acid biosynthesis catalyzed by CYP3A are markedly up-regulated in Cyp27-/- mice but not in cerebrotendinous xanthomatosis.	2001 Sep 14	11454857
Determination of bioactive diterpenoids from Andrographis paniculata by micellar electrokinetic chromatography.	2001 Sep 28	11681575
Toxicity and uptake mechanism of cylindrospermopsin and lophyrotomin in primary rat hepatocytes.	2002 Feb	11689242

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage of CHOLBAM (cholic acid) is 10 to 15 mg/kg administered orally once daily, or in two divided doses, in pediatric patients and in adults.

Route of Administration: Oral

In Vitro Use Guide

25 uM cholic acid significantly upregulated Δ4-3-oxosteroid 5β-reductase member D1 of the aldo-keto reductase family 1 (AKR1D1) expression in HepG2 cells

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:07:25 GMT 2023` Edited by `admin` on `Fri Dec 15 15:07:25 GMT 2023`
Record UNII	G1JO7801AE
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CHOLIC ACID

Official Name

English

3α,7α,12α-Trihydroxy-5β-cholan-24-oic acid

Systematic Name

English

3,7,12-TRIHYDROXYCHOLANIC ACID

Systematic Name

English

CHOLALIC ACID

Common Name

English

CHOLIC ACID [FCC]

Common Name

English

CHOLAN-24-OIC ACID, 3,7,12-TRIHYDROXY-, (3-.ALPHA.,5-.BETA.,7-.ALPHA.,12-.ALPHA.)-

Common Name

English

CHOLAN-24-OIC ACID, 3,7,12-TRIHYDROXY-, (3.ALPHA.,5.BETA.,7.ALPHA.,12.ALPHA.)-

Common Name

English

Cholic acid [WHO-DD]

Common Name

English

URSODEOXYCHOLIC ACID IMPURITY B [EP IMPURITY]

Common Name

English

ORPHACOL

Brand Name

English

CHOLIC ACID [USP-RS]

Common Name

English

CHOLIC ACID [ORANGE BOOK]

Common Name

English

CHOLIC ACID [MI]

Common Name

English

NSC-6135

Code

English

CHOLIC ACID [HSDB]

Common Name

English

CHOLIC ACID [EP IMPURITY]

Common Name

English

CHOLIC ACID [EMA EPAR]

Common Name

English

CHOLBAM

Brand Name

English

CHOLIC ACID [USAN]

Common Name

English

CHOLIC ACID [JAN]

Common Name

English

KOLBAM

Brand Name

English

Classification Tree Code System Code

WHO-ATC

A05AA03