Deoxycholate

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Deoxycholate

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Deoxycholate

Identifiers
Leadscope Id	LS-53044
CAS	83-44-3
ChemSpider	193196
UNII	005990WHZZ
Pathway DBs
Assay DBs
PubChem CID	222528
Omics DBs
Properties
ToxCast Accepted	no
Toxic Effect	Apoptosis
ToxBank Accepted	no
Target	steroid, bile acid

Hepatotoxicity Data
Gold Compound Evaluation and Comments
Calculated/Predicted Properties

Executive Summary

Summary Information

The table listed below contains a summarized listing of toxic effect information leveraged from the 6th European Framework Programme project LIINTOP. For a complete listing of the Gold Compound evaluation criteria please see the Gold Compound Evaluation and Comments immediately following the summary table below.

SMILES	CC(CCC(=O)[O-])C1CCC2C1(C(CC3C2CCC4C3(CCC(C4)O)C)O)C.[Na+]
InChI	InChI=1S/C24H40O4.Na/c1-14(4-9-22(27)28)18-7-8-19-17-6-5-15-12-16(25)10-11-23(15,2)20(17)13-21(26)24(18,19)3;/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
InChI-Key	FHHPUSMSKHSNKW-SMOYURAASA-M
Supplier	Sigma Aldrich

Summary Hepatotoxic Effects from the LIINTOP FP6 Program

References

+

^[1] ^[2] ^[3] ^[4] ^[5]

The following table is organized into four main sections and provides a detailed assessment by the Gold Compound Working Group for the use of this compound as a standard hepatotoxin. The table's four sections (collapsed by default but will expand when the "show" link is clicked) contains detailed information for the core set of SEURAT compound acceptance criteria.

Standard to Meet

Compound Assessment

Human Toxicity
Compound causes one or more of the following: cholestasis steatosis phospholipidosis fibrosis cell death in humans; or exemplifies an in vitro mechanism underlying one of these toxicities.
Toxicity occurs via one or more of the following mechanisms: mitochondrial disruption inhibition of lipid transport or metabolism nuclear receptor modulation complexation of phospholipids
Therapeutic target.
Biochemical mechanism of toxicity.

PK-ADME
PK parameters ¹: recommended dose C_max Vd half-life
Therapeutic window.¹
Metabolically activated (optional), active metabolite known and available for testing.²

Omics and IC50 Data
Gene expression profiles known.³
Proteomics profiles known.³
Metabonomics profiles known.³
Fluxomics profiles known.³
Epigenomics profiles known.³
Observed IC₅₀ for in vitro cellular efficacy.⁴
Observed IC₅₀ for in vitro cellular toxicity studies. ⁴

Physical Properties
Accepted and listed within the ToxCast/Tox21 program.⁵
Defined and confirmed structure and isomeric form(s).
Substance stability.
Soluble in buffer solution at 30 times the in vitro IC₅₀ for toxicity.⁶
Solubility in DMSO 100 times buffer solubility.
Vessel binding properties.⁷
Commercial availability at > 95% (> 99% is preferred).
Vapor pressure. (Non-volatile)

Criteria Notes

1.	The in vivo therapeutic window is used to estimate an appropriate concentration for in vitro toxicity assays. This in vitro concentration should also be consistent with the exposure implied by pharmacokinetics parameters.
2.	We prefer compounds that require metabolic activation, although standards that are active in themselves will be accepted if they have otherwise valuable properties. We require knowing the active metabolite, and we prefer compounds where the metabolite is stable and can be independently tested in order to verify the mechanism of toxicity as well as of metabolic activation in the test cell line.
3.	Literature data for at least one, but not necessarily all, of the ‘omics datasets is desired. This requirement can be waived in special cases.
4.	The IC₅₀’s for in vitro efficacy and toxicity should be consistent with the therapeutic ratio observed in the clinic. These parameters will be dependent on specific cell type and culture conditions, but differences of more than 30-fold in the in vitro vs. in vivo therapeutic ratios should be considered suspect and carefully justified.
5.	This is not a requirement, but compounds utilized in the EPA testing program can be assumed to have physical properties verified to be suitable for in vitro cellular assays.
6.	Sparing soluble compounds may be assayed for solubility in serum and the percent serum used specified here.
7.	This property will be measured when a sample of compound becomes available.

Proprietary Toxicity Literature Report

The toxicity literature report contains proprietary information and references for studies performed on this compound relevant to liver toxicity findings and is restricted for use within the SEURAT program only.

Toxicity Report

PubMed references

The following resource link will perform a PubMed query for the terms "Deoxycholate" and "liver toxicity".
Deoxycholate Search

References

↑ Feldmann, G., 2006. Liver apoptosis. Gastroenterol. Clin. Biol. 30, 533–545.
↑ Gomez-Lechon, M.J., O’Connor, E., Castell, J.V., Jover, R., 2002. Sensitive markers used to identify compounds that trigger apoptosis in cultured hepatocytes. Toxicol. Sci. 65, 299–308.
↑ Gomez-Lechon, M.J., O’Connor, J.E., Lahoz, A., Castell, J.V., Donato, M.T., 2008. Identification of apoptotic drugs: multiparametric evaluation in cultured hepatocytes. Curr. Med. Chem. 15, 2071–2085.
↑ Gomez-Lechon, M.J., Ponsoda, X., O’Connor, E., Donato, T., Jover, R., Castell, J.V., 2003. Diclofenac induces apoptosis in hepatocytes. Toxicol. in Vitro 17, 675– 680.
↑ Kass, G.E., Macanas-Pirard, P., Lee, P.C., Hinton, R.H., 2003. The role of apoptosis in acetaminophen-induced injury. Ann. NY Acad. Sci. 1010, 557–559.

Calculated/Predicted Properties

Water Solubility Results

pH

Sol,mg/ml

0

Graph

2

37.08

100

5.5

37.08

100

6.5

37.08

100

7.4

37.08

100

10

37.08

100

Summary Solubility Data

Intrinsic Solubility,mg/ml	37.0802
Intrinsic Solubility,log(S,mol/l)	-0.6836
Solubility in Pure Water at pH = 7,mg/ml	37.0802

Calculations performed using ACD/PhysChem v 9.14

LogD Results
pH	LogD	Graph
2	0.86
5.5	0.86
6.5	0.86
7.4	0.86
10	0.86
Calculations performed using ACD/PhysChem v 9.14

Single-valued Properties
Property	Value	Units	Error
LogP	0.86		0.68
MW	178.95		-
PSA	18.46		-
FRB	0		-
HDonors	0		-
HAcceptors	2		-
Rule Of 5	0		-
Molar Refractivity	27.24	cm³	0.4
Molar Volume	107.76	cm³	5
Parachor	249.5	cm³	6
Index of Refraction	1.42		3.33E^-2
Surface Tension	28.74	dyne/cm	5
Density	1.66	g/cm³	0.1
Polarizability	10.8	10E^-24 cm³	0.5
Calculations performed using ACD/PhysChem v 9.14

Property Name	Value	Units	Source
pKa	-		SPARC v4.5
Estimated VP	4.36	mm Hg	EPI Suite v4.10
Estimated VP	581.3	Pa	EPI Suite v4.10
Estimated Water Solubility	8971	mg/L	EPI Suite v4.10
WATERNT Frag Water Solubility Estimate	20253	mg/L	EPI Suite v4.10

pKa Results
Acidic/Basic	Acidic/Basic	Aparrent pKa Value	Error
A = Acidic B = Basic MA = Most Acidic MB = Most Basic
Calculations performed using ACD/PhysChem v 9.14

Authors of this ToxBank wiki page

David Bower, Egon Willighagen, Matthew Clark

Facts about DeoxycholateRDF feed

Accepted by ToxBank	no +
Accepted by ToxCast	no +
Equivalent URIThis property is a special property in this wiki.	http://bio2rdf.org/cas:83-44-3 +, http://www.chemspider.com/Chemical-Structure.193196.rdf +, http://bio2rdf.org/pubchem:222528 +, and http://rdf.openmolecules.net/?InChI=1S/C24H40O4.Na/c1-14(4-9-22(27)28)18-7-8-19-17-6-5-15-12-16(25)10-11-23(15,2)20(17)13-21(26)24(18,19)3;/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 +
Has CAS	83-44-3 +
Has ChemSpider Id	193196 +
Has InChI	InChI=1S/C24H40O4.Na/c1-14(4-9-22(27)28)18-7-8-19-17-6-5-15-12-16(25)10-11-23(15,2)20(17)13-21(26)24(18,19)3;/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 +
Has InChIKey	FHHPUSMSKHSNKW-SMOYURAASA-M +
Has Leadscope Id	LS-53044 +
Has PubChem CID	222528 +
Has Smiles	O1C(O[C@@H]([C@@H]1Cl)Cl)(F)F +
Has category	Hepatotoxic +
Has image	Deoxycholate.png +
Has target	steroid, bile acid +
Has toxic effect	Apoptosis +

[ref-1-0] Feldmann, G., 2006. Liver apoptosis. Gastroenterol. Clin. Biol. 30, 533–545.

[ref-2-1] Gomez-Lechon, M.J., O’Connor, E., Castell, J.V., Jover, R., 2002. Sensitive markers used to identify compounds that trigger apoptosis in cultured hepatocytes. Toxicol. Sci. 65, 299–308.

[ref-3-2] Gomez-Lechon, M.J., O’Connor, J.E., Lahoz, A., Castell, J.V., Donato, M.T., 2008. Identification of apoptotic drugs: multiparametric evaluation in cultured hepatocytes. Curr. Med. Chem. 15, 2071–2085.

[ref-4-3] Gomez-Lechon, M.J., Ponsoda, X., O’Connor, E., Donato, T., Jover, R., Castell, J.V., 2003. Diclofenac induces apoptosis in hepatocytes. Toxicol. in Vitro 17, 675– 680.

[ref-5-4] Kass, G.E., Macanas-Pirard, P., Lee, P.C., Hinton, R.H., 2003. The role of apoptosis in acetaminophen-induced injury. Ann. NY Acad. Sci. 1010, 557–559.

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[2]

[3]

[4]

[5]

Deoxycholate

From ToxBankWiki

Executive Summary

Summary Information

Proprietary Toxicity Literature Report

PubMed references

References

Calculated/Predicted Properties

Authors of this ToxBank wiki page

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