SODIUM HYODEOXYCHOLATE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H39O4.Na
Molecular Weight	414.5538
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=DUYSCILLIVEITB-ADQIWYCWSA-M

InChI=1S/C24H40O4.Na/c1-14(4-7-22(27)28)17-5-6-18-16-13-21(26)20-12-15(25)8-10-24(20,3)19(16)9-11-23(17,18)2;/h14-21,25-26H,4-13H2,1-3H3,(H,27,28);/q;+1/p-1/t14-,15-,16+,17-,18+,19+,20+,21+,23-,24-;/m1./s1

HIDE SMILES / InChI

Description
Sources: http://cdn2.hubspot.net/hub/150154/file-473189780-pdf/docs/AtheroNova-AHRO-Executive-Informational-Overview2-01-22-2014.pdf
Curator's Comment: description was created based on several sources, including: https://en.wikipedia.org/wiki/Hyodeoxycholic_acid | https://cdn2.hubspot.net/hub/150154/file-27656828-pdf/docs/atheronova-ahro-quarterly-update-04-05-2013.pdf | https://www.ncbi.nlm.nih.gov/pubmed/10936612

Hyodeoxycholic acid, also known as HDCA, is a secondary bile acid. Natural 6alpha-hydroxylated bile acids are receptor-specific activators of nuclear liver X receptor alpha (LXRalpha), a nuclear receptor regulating the expression of the cholesterol 7alpha-hydroxylase gene. AHRO-001 (Hyodeoxycholic acid) is in phase I clinical trials for the treatment of atherosclerosis. Through a complex signaling processes utilizing LXR receptors, the compound is designed to increase the efficiency of cholesterol efflux using the HDL cells, which act on all cholesterol in the arterial circulation as well as in the lipid core of plaque deposits in the artery walls. Use of AHRO-001 has shown no adverse effects on morbidity, mortality or toxicity and has been well tolerated at high doses.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
LXR-alpha 10 Target ID: CHEMBL2808 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10936612	Agonist 2678
UDP-glucuronosyltransferase 2B7 4 Target ID: CHEMBL4370 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12527334	Substrate 661
UDP-glucuronosyltransferase 2B4 3 Target ID: CHEMBL6196 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8244999	Substrate 661

Conditions

Condition	Modality	Targets	Highest Phase	Product
Atherosclerosis 74 Sources: http://adisinsight.springer.com/drugs/800038244 https://www.ncbi.nlm.nih.gov/pubmed/23752203	Primary		Phase I 428	Unknown Approved Use Unknown
Hypercholesterolemia 47 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7619860 http://adisinsight.springer.com/trials/700206192	Primary		Phase I 428	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
3344 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16750434	3.44 mg/kg single, intraperitoneal dose: 3.44 mg/kg route of administration: Intraperitoneal experiment type: SINGLE co-administered: GENIPOSIDE\|Isoniazid\|Cholic acid	GENIPOSIDE\|Isoniazid\|Cholic acid	HYODEOXYCHOLIC ACID plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.121 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16750434	3.44 mg/kg single, intraperitoneal dose: 3.44 mg/kg route of administration: Intraperitoneal experiment type: SINGLE co-administered: GENIPOSIDE\|Isoniazid\|Cholic acid	GENIPOSIDE\|Isoniazid\|Cholic acid	HYODEOXYCHOLIC ACID plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	UGT1A10 291 UGT2B4 249 UGT2A2 48 UGT2A1 32 UGT8 2 UGT2B7 389 UGT1A8 283 UGT1A1 418 UGT2A3 48 UGT 192 UGT1A3 422 UGT2B28 63 UGT1A7 236 UGT2B10 127 UGT2B15 203 UGT2B17 213 P-gp 1537

Drug as victim

Target	Modality	Activity
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12527334/	likely
UGT2A3 48	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23756265/	likely
UGT2B28 63	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12527334/	likely
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680132	no
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	no
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	no
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	no
UGT2B10 127	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	no
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	no
UGT2B17 213	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10836148/	no
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12527334/ \| https://pubmed.ncbi.nlm.nih.gov/23756265/	weak
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12527334/ \| https://pubmed.ncbi.nlm.nih.gov/23756265/	yes [Km 11.6 uM]
UGT 192	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/1909626/	yes [Km 12 uM]
UGT2A2 48	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23756265/	yes [Km 150.4 uM]
UGT2A1 32	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23756265/	yes [Km 178.5 uM]
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12527334/ \| https://pubmed.ncbi.nlm.nih.gov/23756265/	yes
UGT8 2	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25519837/	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003RFW	https://www.1pchem.com/search?query=1P003RFW
A2B Chem	AB74732	http://a2bchem.com/prod/AB74732
AK Scientific	0003TG	https://aksci.com/item_detail.php?cat=0003TG
AK Scientific	H106	https://aksci.com/item_detail.php?cat=H106
AK Scientific	J91554	https://aksci.com/item_detail.php?cat=J91554
AK Scientific	J92519	https://aksci.com/item_detail.php?cat=J92519
AK Scientific	K489	https://aksci.com/item_detail.php?cat=K489
AstaTech	43086	http://astatechinc.com/CPSResult.php?CRNO=43086
BOC Sciences	10421-49-5	http://www.bocsci.com/description.asp?cas=10421-49-5
BioSynth	W-104141	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-104141
Cayman Chemical	20294	http://www.caymanchem.com/app/template/Product.vm/catalog/20294
Chem Scene	CS-0007886	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0007886
Chem-Impex International	29962	http://www.chemimpex.com/category/search/29962/2?filter=&search=29962&type=q&keywordoption=ANY&cid=2&fltrdesc=
Chem-Impex International	31890	http://www.chemimpex.com/category/search/31890/2?filter=&search=31890&type=q&keywordoption=ANY&cid=2&fltrdesc=
ChemShuttle	112189	https://www.chemshuttle.com/catalogsearch/result/?q=112189
Combi-Blocks	QA-8913	http://www.combi-blocks.com/cgi-bin/find.cgi?QA-8913
Fluorochem	516405	http://www.fluorochem.co.uk/Products/Product?code=516405
KeyOrganics	AS-14254	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-14254
KeyOrganics	AS-60591	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-60591
Lab Network	LN01285032	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01285032
Lab Network	LN01352348	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01352348
Matrix Scientific	98473	http://www.matrixscientific.com/098473.html
MedChem Express	HY-N0169	https://www.medchemexpress.com/search.html?q=HY-N0169&ft=&fa=&fp=
MolPort	MolPort-016-633-329	https://www.molport.com/shop/molecule-link/MolPort-016-633-329
MolPort	MolPort-023-220-260	https://www.molport.com/shop/molecule-link/MolPort-023-220-260
Molnova	M19159	https://www.molnova.com/en/serch-list.html?keywords=M19159
Selleck Chemicals	S2311	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2311
TargetMol	83-49-8	https://www.targetmol.com/search?keyword=83-49-8
TargetMol	HMDB0000733	https://www.targetmol.com/search?keyword=HMDB0000733
TargetMol	T2968	https://www.targetmol.com/search?keyword=T2968
Tetrahedron	TS09187	http://www.thsci.com/search.do?q=TS09187
Tetrahedron	TS69717	http://www.thsci.com/search.do?q=TS69717
Toronto Research Chemicals	H998100	https://www.trc-canada.com/product-detail/?CatNum=H998100
W&J PharmaChem	50A573126	http://wjpharmachem.com/new/searcht.php?keyword=50A573126
W&J PharmaChem	50C163273	http://wjpharmachem.com/new/searcht.php?keyword=50C163273
eMolecules	300679078	https://orderbb.emolecules.com/search/#?query=300679078
eMolecules	30151939	https://orderbb.emolecules.com/search/#?query=30151939
eMolecules	43470322	https://orderbb.emolecules.com/search/#?query=43470322
eMolecules	50505823	https://orderbb.emolecules.com/search/#?query=50505823
eNovation Chemicals	D659533	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D659533&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6151721743	https://mcule.com/MCULE-6151721743/
mcule	MCULE-6751073161	https://mcule.com/MCULE-6751073161/
mcule	MCULE-7294774452	https://mcule.com/MCULE-7294774452/

PubMed

Title	Date	PubMed
Isolation and characterization of hyodeoxycholic-acid: UDP-glucuronosyltransferase from human liver.	1991 Sep 1	1909626
Reinduction of the hypnotic effects of thiopental with NSAIDs by decreasing thiopental plasma protein binding in humans.	1993 Apr	8517101
Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs.	1993 Jan	8423545
UGT2B23, a novel uridine diphosphate-glucuronosyltransferase enzyme expressed in steroid target tissues that conjugates androgen and estrogen metabolites.	1999 Dec	10579317
Hyodeoxycholic acid efficiently suppresses atherosclerosis formation and plasma cholesterol levels in mice.	2001 Aug	11483626
Effect of bile salts on colonic mucus secretion in isolated vascularly perfused rat colon.	2001 Jun	11414298
Hydrophilic and hydrophobic bile acids exhibit different cytotoxicities through cytolysis, interleukin-8 synthesis and apoptosis in the intestinal epithelial cell lines. IEC-6 and Caco-2 cells.	2001 May	11346209
[Study on effect of qingkailing injection and its active principle in inducing cell apoptosis in human acute promyelocytic leukemia].	2001 Nov	12575380
Dietary bile acids inhibit potentially elemental diet-induced small intestinal atrophy in rats.	2002 Nov	12373304
Peroxisome proliferator-activated receptor alpha induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme.	2003 Aug 29	12810707
Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7.	2003 Feb 1	12527334
Steroids in the intestinal tract of rats are affected by dietary-fibre-rich barley-based diets.	2003 Nov	14667183
Substrate specificities of rat oatp1 and ntcp: implications for hepatic organic anion uptake.	2003 Nov	12842829
UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients.	2004	15318931
Identification of UGT2B9*2 and UGT2B33 isolated from female rhesus monkey liver.	2004 Jun 1	15130782
[Study on extraction technique of HDCA].	2004 May	15706890
Effects of ileo-rectal anastomosis on cholesterol metabolism in pigs fed either casein or extruded soya beans.	2004 May	15137920
Effect of dried plums on colon cancer risk factors in rats.	2005	16351514
Interfacial properties of most monofluorinated bile acids deviate markedly from the natural congeners: studies with the Langmuir-Pockels surface balance.	2005 Mar	15604514
Simultaneous determination of major bioactive components in Qingkailing injection by high-performance liquid chromatography with evaporative light scattering detection.	2005 Nov	16272719
[Simultaneous determination of five groups of components in qingkailing injection by high performance liquid chromatography with photo diode array detector and evaporative light scattering detector].	2005 Sep	16350790
Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides.	2006 Apr	16225954
3alpha-6alpha-Dihydroxy-7alpha-fluoro-5beta-cholanoate (UPF-680), physicochemical and physiological properties of a new fluorinated bile acid that prevents 17alpha-ethynyl-estradiol-induced cholestasis in rats.	2006 Jul 15	16487557
Isolation and determination of bile acids.	2006 Jul-Sep	17136860
Determination of three bile acids in artificial Calculus Bovis and its medicinal preparations by micellar electrokinetic capillary electrophoresis.	2006 Jun 6	16651035
Simultaneous determination of nine components in Qingkailing injection by HPLC/ELSD/DAD and its application to the quality control.	2006 Mar 3	16257167
Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity.	2006 Sep 1	16948850
Simultaneous determination of geniposide, baicalin, cholic acid and hyodeoxycholic acid in rat serum for the pharmacokinetic investigations by high performance liquid chromatography-tandem mass spectrometry.	2006 Sep 14	16750434
[Determination of chyodeoxycholic acid in Bile Arisaema by HPLC-ELSD].	2007 Aug	18027654
Comparative study on major bioactive components in natural, artificial and in-vitro cultured Calculus Bovis.	2007 Jan	17202716
Use of selected chemical markers in combination with a multiple regression model to assess the contribution of domesticated animal sources of fecal pollution in the environment.	2007 Nov	17590407
Biotransformation of lithocholic acid by rat hepatic microsomes: metabolite analysis by liquid chromatography/mass spectrometry.	2008 Feb	18039809
Novel polymorphic human UDP-glucuronosyltransferase 2A3: cloning, functional characterization of enzyme variants, comparative tissue expression, and gene induction.	2008 Sep	18523138
Regulation of sulfotransferase and UDP-glucuronosyltransferase gene expression by the PPARs.	2009	19680455
Challenges predicting ligand-receptor interactions of promiscuous proteins: the nuclear receptor PXR.	2009 Dec	20011107
Improved analysis of bile acids in tissues and intestinal contents of rats using LC/ESI-MS.	2009 Jan	18772484
The inhibitory effects of cholalic acid and hyodeoxycholalic acid on the expression of TNFalpha and IL-1beta after cerebral ischemia in rats.	2009 Jan	19183878
Bear bile: dilemma of traditional medicinal use and animal protection.	2009 Jan 12	19138420
Serum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inflammatory bowel disease.	2009 Jul 7	19575493
3-ketocholanoic acid is the major in vitro human hepatic microsomal metabolite of lithocholic acid.	2009 Sep	19487251
Consumption of some polyphenols reduces fecal deoxycholic acid and lithocholic acid, the secondary bile acids of risk factors of colon cancer.	2009 Sep 23	19711910
Liver X receptor agonist methyl-3β-hydroxy-5α,6α-epoxycholanate attenuates atherosclerosis in apolipoprotein E knockout mice without increasing plasma triglyceride.	2010	21071998
Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes.	2010 Jul	20622262
Identification of human UGT2B7 as the major isoform involved in the O-glucuronidation of chloramphenicol.	2010 Mar	20008037
Regulation of bile acid synthesis by fat-soluble vitamins A and D.	2010 May 7	20233723
Voluntary wheel running exercise and dietary lactose concomitantly reduce proportion of secondary bile acids in rat feces.	2010 Sep	20616226
Inhibition of human UGT2B7 gene expression in transgenic mice by the constitutive androstane receptor.	2011 Jun	21415305

Patents

Sample Use Guides

In Vivo Use Guide

Cohort 1: 500 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 2: 750 mg/dose, given as a single dose then as bid x7days and tid x 7days Cohort 3: 1000 mg/dose, given as a single dose then as bid x7days and tid x7days Cohort 4: 21 days dosing given at best tolerated dose determined by cohorts 1-3 Cohort 5: 12 wks dosing given at best tolerated dose determined by cohorts 1-4

Route of Administration: Oral

In Vitro Use Guide

HDCA treatment (50 and 100 uM) significantly increased the expression of ATP-binding cassette subfamily A member 1 (Abca1), ATP-binding cassette subfamily G member 1 (Abcg1), and apolipoprotein E (Apoe) in RAW cells in a dose-response way.

Name

Type

Language

SODIUM HYODEOXYCHOLATE

Common Name

English

CHOLAN-24-OIC ACID, 3,6-DIHYDROXY-, SODIUM SALT (1:1), (3.ALPHA.,5.BETA.,6.ALPHA.)-

Systematic Name

English

SODIUM HYODESOXYCHOLATE

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID60908871