SODIUM CHOLATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H39O5.Na
Molecular Weight	430.5532
Optical Activity	UNSPECIFIED
Defined Stereocenters	11 / 11
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[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=NRHMKIHPTBHXPF-TUJRSCDTSA-M

InChI=1S/C24H40O5.Na/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);/q;+1/p-1/t13-,14+,15-,16-,17+,18+,19-,20+,22+,23+,24-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	C24H39O5
Molecular Weight	407.5635
Charge	-1
Count

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

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
Role of phospholipids in reconstituted cytochrome P450 3A form and mechanism of their activation of catalytic activity.	1992 Jul 7	1627548
Bile acids: natural ligands for an orphan nuclear receptor.	1999 May 21	10334993
Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4.	2000 May 19	10809780
Bile acid acyl adenylate: a possible intermediate to produce a protein-bound bile acid.	2001	11180537
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
Bile acid-oligodeoxynucleotide conjugates: synthesis and liver excretion in rats.	2001 Apr 9	11294397
Effect of bile acids on formation of azoxymethane-induced aberrant crypt foci in colostomized F344 rat colon.	2001 Aug 28	11431100
Bile acid metabolism by fresh human colonic contents: a comparison of caecal versus faecal samples.	2001 Dec	11709519
Alterations in intestinal microflora, faecal bile acids and short chain fatty acids in dextran sulphate sodium-induced experimental acute colitis in rats.	2001 Feb	11246608
Paradoxical increase in nitric oxide synthase activity in hypercholesterolaemic rats with impaired renal function and decreased activity of nitric oxide.	2001 Feb	11158398
Effect of bile acids on the uptake of irinotecan and its active metabolite, SN-38, by intestinal cells.	2001 Feb 16	11342261
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
Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver.	2001 Jul	11438506
Separation and selectivity of benzophenones in micellar electrokinetic chromatography using sodium dodecyl sulfate micelles or sodium cholate modified mixed micelles.	2001 Jul 20	11510546
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
Molecular umbrella-assisted transport of glutathione across a phospholipid membrane.	2001 Jun 13	11389618
Bilirubin-induced apoptosis in cultured rat neural cells is aggravated by chenodeoxycholic acid but prevented by ursodeoxycholic acid.	2001 Mar	11322201
Ursodeoxycholic acid administration in patients with cholestasis of pregnancy: effects on primary bile acids in babies and mothers.	2001 Mar	11230728
Structural consequences of metal complexation of cyclo[Pro-Phe-Phe-Ala-Xaa]2 decapeptides.	2001 Mar 16	11322543
Design and synthesis of novel chiral dendritic species derived from bile acids.	2001 May 4	11325268
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
In vitro excystation of Paragonimus heterotremus metacercariae.	2001 Oct	11695393
Potency of select statin drugs in a new mouse model of hyperlipidemia and atherosclerosis.	2001 Oct 23	11604260
Toxicity and uptake mechanism of cylindrospermopsin and lophyrotomin in primary rat hepatocytes.	2002 Feb	11689242
The association of manganese superoxide dismutase expression in Barrett's esophageal progression with MnTBAP and curcumin oil therapy.	2012 Aug	22316666
An Atherogenic Paigen-Diet Aggravates Nephropathy in Type 2 Diabetic OLETF Rats.	2015	26606054

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 15:11:48 GMT 2023` Edited by `admin` on `Fri Dec 15 15:11:48 GMT 2023`
Record UNII	NU3Y4CCH8Z
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

SODIUM CHOLATE

Official Name

English

Cholate sodium [WHO-DD]

Common Name

English

CHOLATE SODIUM

Common Name

English

CHOLIC ACID, SODIUM SALT

Common Name

English

SODIUM CHOLATE [INCI]

Common Name

English

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

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID9033979