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

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
Validity and sensitivity of an intravenous bile acid tolerance test in patients with liver disease.	1975 Jun 5	1128572
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
Physicochemical properties of liposomes incorporating hydrochlorothiazide and chlorothiazide.	2001	11378524
Characterization, stability and in-vivo distribution of asialofetuin glycopeptide incorporating DSPC/CHOL liposomes prepared by mild cholate incubation.	2001 Apr	11697109
Separation of neutral compounds by microemulsion electrokinetic chromatography: fundamental studies on selectivity.	2001 Apr	11379955
The effect of absorption enhancers on the initial degradation kinetics of insulin by alpha-chymotrypsin.	2001 Apr 17	11292547
Design of rolipram-loaded nanoparticles: comparison of two preparation methods.	2001 Apr 28	11295222
Metabolism and effects on cholestasis of isoursodeoxycholic and ursodeoxycholic acids in bile duct ligated rats.	2001 Apr 3	11287121
Bile acid-oligodeoxynucleotide conjugates: synthesis and liver excretion in rats.	2001 Apr 9	11294397
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
Bile acid metabolism by fresh human colonic contents: a comparison of caecal versus faecal samples.	2001 Dec	11709519
Study of partition of nitrazepam in bile salt micelles and the role of lecithin.	2001 Feb	11272316
Determination of alkylphenol ethoxylates by micellar electrokinetic chromatography with bile salts.	2001 Feb	11258765
Effect of bile acids on the uptake of irinotecan and its active metabolite, SN-38, by intestinal cells.	2001 Feb 16	11342261
Enzymatic syntheses of T antigen-containing glycolipid mimicry using the transglycosylation activity of endo-alpha-N-acetylgalactosaminidase.	2001 Feb 28	11269400
Mitochondrial medicine--molecular pathology of defective oxidative phosphorylation.	2001 Jan	11314862
Enzymatic synthesis of aliphatic beta-lactosides as mimic units of glycosphingolipids by use of Trichoderma reesei cellulase.	2001 Jan 1	11361028
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
Transmembrane ion channels constructed of cholic acid derivatives.	2001 Jul 27	11463261
The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor.	2001 Jul 6	11331284
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
Transcriptional regulation of the human sterol 27-hydroxylase gene (CYP27) and promoter mapping.	2001 Jun	11395030
Development and validation of a cholate binding capacity method for DMP 504, a bile acid sequestrant.	2001 Jun	11377012
Deoxycholic acid suppresses p53 by stimulating proteasome-mediated p53 protein degradation.	2001 Jun	11375905
Characterization of the promoter region of the human peroxisomal multifunctional enzyme type 2 gene.	2001 Jun 1	11374894
Molecular umbrella-assisted transport of glutathione across a phospholipid membrane.	2001 Jun 13	11389618
Surfactant, but not the size of solid lipid nanoparticles (SLN) influences viability and cytokine production of macrophages.	2001 Jun 19	11397567
Antiatherogenic effects of 17 beta-estradiol and 17 alpha-estradiol and its derivative J811 in cholesterol-fed rabbits with thyroid inhibition.	2001 Mar	11379378
[3-oxo-delta 4-steroid 5 beta-reductase deficiency].	2001 Mar	11347080
[3 beta-Hydroxysteroid-delta 5-oxidoreductase/isomerase deficiency].	2001 Mar	11347079
Bilirubin-induced apoptosis in cultured rat neural cells is aggravated by chenodeoxycholic acid but prevented by ursodeoxycholic acid.	2001 Mar	11322201
Structural consequences of metal complexation of cyclo[Pro-Phe-Phe-Ala-Xaa]2 decapeptides.	2001 Mar 16	11322543
Activities of cholic acid-derived antimicrobial agents against multidrug-resistant bacteria.	2001 May	11328782
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.	2001 May	11306713
Characterization of expressed full-length and truncated FMO2 from rhesus monkey.	2001 May	11302936
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
Design and synthesis of novel chiral dendritic species derived from bile acids.	2001 May 4	11325268
Efficient gene delivery via non-covalent complexes of folic acid and polyethylenimine.	2001 Nov 9	11689266
Human liver UDP-glucuronosyltransferase isoforms involved in the glucuronidation of 7-ethyl-10-hydroxycamptothecin.	2001 Oct	11695848
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
Effect of different bile salts on the relative hypoglycemia of witepsol W35 suppositories containing insulin in diabetic Beagle dogs.	2001 Sep	11699836
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

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

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