ELLAGIC ACID

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H6O8
Molecular Weight	302.1926
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=C(O)C2=C3C(=C1)C(=O)OC4=C3C(=CC(O)=C4O)C(=O)O2

InChI

InChIKey=AFSDNFLWKVMVRB-UHFFFAOYSA-N

InChI=1S/C14H6O8/c15-5-1-3-7-8-4(14(20)22-11(7)9(5)17)2-6(16)10(18)12(8)21-13(3)19/h1-2,15-18H

HIDE SMILES / InChI

Molecular Formula	C14H6O8
Molecular Weight	302.1926
Charge	0
Count

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

Description
Sources: https://www.drugbank.ca/drugs/DB08846
Curator's Comment: Ellagic acid is a dilactone of hexahydroxydiphenic acid, that found in numerous fruits and vegetables. Ellagic acid was first discovered by chemist Henri Braconnot in 1831. Ellagic acid is found in oaks species like the North American white oak (Quercus alba) and European red oak (Quercus robur). The highest levels of ellagic acid are found in walnuts, pecans, cranberries, raspberries, strawberries, and grapes, as well as distilled beverages. It is also found in peach, and other plant foods. Ellagic acid has antiproliferative and antioxidant properties in a number of in vitro and small-animal models. The antiproliferative properties of ellagic acid may be due to its ability to directly inhibit the DNA binding of certain carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons. As with other polyphenol antioxidants, ellagic acid has a chemoprotective effect in cellular models by reducing oxidative stress. Ellagic acid is an investigational drug studied for treatment of Follicular Lymphoma (phase 2 trial), protection from brain injury of intrauterine growth restricted babies (phase 1 and 2 trial), improvement of cardiovascular function in adolescents who are obese (phase 2 trial), and topical treatment of solar lentigines. Ellagic acid has been marketed as a dietary supplement with a range of claimed benefits against cancer, heart disease, and other medical problems. Ellagic acid has been identified by the U.S. Food and Drug Administration as a "fake cancer 'cure' consumers should avoid".

Ellagic acid is a dilactone of hexahydroxydiphenic acid, that found in numerous fruits and vegetables. Ellagic acid was first discovered by chemist Henri Braconnot in 1831. Ellagic acid is found in oaks species like the North American white oak (Quercus alba) and European red oak (Quercus robur). The highest levels of ellagic acid are found in walnuts, pecans, cranberries, raspberries, strawberries, and grapes, as well as distilled beverages. It is also found in peach, and other plant foods. Ellagic acid has antiproliferative and antioxidant properties in a number of in vitro and small-animal models. The antiproliferative properties of ellagic acid may be due to its ability to directly inhibit the DNA binding of certain carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons. As with other polyphenol antioxidants, ellagic acid has a chemoprotective effect in cellular models by reducing oxidative stress. Ellagic acid is an investigational drug studied for treatment of Follicular Lymphoma (phase 2 trial), protection from brain injury of intrauterine growth restricted babies (phase 1 and 2 trial), improvement of cardiovascular function in adolescents who are obese (phase 2 trial), and topical treatment of solar lentigines. Ellagic acid has been marketed as a dietary supplement with a range of claimed benefits against cancer, heart disease, and other medical problems. Ellagic acid has been identified by the U.S. Food and Drug Administration as a "fake cancer 'cure' consumers should avoid".

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Casein kinase II alpha 3 Target ID: CHEMBL3629 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19414254	Inhibitor 8146	40.0 nM [IC50]
Aldose reductase 44 Target ID: CHEMBL1900 Sources: http://www.ncbi.nlm.nih.gov/pubmed/22377675	Inhibitor 8146	200.0 nM [IC50]
Tyrosine-protein kinase TIE-2 6 Target ID: CHEMBL4128 Sources: http://www.ncbi.nlm.nih.gov/pubmed/22377675	Inhibitor 8146	260.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Follicular lymphoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00455416	Primary		Phase II 1133	Unknown Approved Use Unknown
HPV infection 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02263378	Primary		Not Provided 505	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3.25 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16172180	13.5 mg 1 times / day multiple, oral dose: 13.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELLAGIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
200.2 ng/mL EXPERIMENT https://scialert.net/abstract/?doi=pjn.2009.1661.1664	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		ELLAGIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
17.61 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16172180	13.5 mg 1 times / day multiple, oral dose: 13.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELLAGIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1041.8 ng × h/mL EXPERIMENT https://scialert.net/abstract/?doi=pjn.2009.1661.1664	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		ELLAGIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.57 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16172180	13.5 mg 1 times / day multiple, oral dose: 13.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELLAGIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8.4 h EXPERIMENT https://scialert.net/abstract/?doi=pjn.2009.1661.1664	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		ELLAGIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
50% EXPERIMENT https://scialert.net/abstract/?doi=pjn.2009.1661.1664	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		ELLAGIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2E1 846 CYP1A1 104 CYP2B1 14 CYP3A1/2 1 OAT1 584 OAT4 145 P-gp 1401 BCRP 678		CYP1A1 103 UGT1A10 9

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 751	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476959/	no
CYP3A1/2 4	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	no
P-gp 1588	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476959/; https://www.degruyter.com/document/doi/10.1515/dmpt-2018-0020/html	no	yes (co-administration study) Comment: The increase in Cmax, AUC, AUMC, AUCtotal and t1/2 of linagliptin was found to be 2.0-fold, 1.2-fold, 1.74- fold, 1.52-fold and 0.5-fold, respectively, in the EA pretreated group compared with the control group. In vitro experiments showed no inhibition Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476959/; https://www.degruyter.com/document/doi/10.1515/dmpt-2018-0020/html
OAT4 145	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15870380/ Page: 3.0	weak [Inhibition 35 uM]
OAT1 588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15870380/ Page: 3.0	yes [IC50 0.207 uM]
CYP1A1 206	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP2B1 39	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP2E1 929	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/8625497/ Page: 1.0	yes [Inhibition 100 uM]
CYP1A1 206	inducer 1515 Sources: https://pubmed.ncbi.nlm.nih.gov/19469472/	yes
UGT1A10 41	inducer 1515 Sources: https://pubmed.ncbi.nlm.nih.gov/19469472/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4775	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4775
ChemicalBook	CB6214708	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6214708
MolPort	MolPort-000-861-050	https://www.molport.com/shop/molecule-link/MolPort-000-861-050
Selleck Chemicals	Ellagic-acid	http://www.selleckchem.com/products/Ellagic-acid.html
ZINC	ZINC000003872446	http://zinc15.docking.org/substances/ZINC000003872446
eMolecules	509332	https://www.emolecules.com/cgi-bin/more?vid=509332

PubMed

Title	Date	PubMed
Ellagitannins and hexahydroxydiphenoyl esters as inhibitors of vertebrate squalene epoxidase.	2001 Aug	11520216
Application of Eudragit P-4135F for the delivery of ellagic acid to the rat lower small intestine.	2001 Aug	11518017
An ellagic compound and iridoids from Cornus capitata root cultures.	2001 Aug	11454361
Chemoprevention of esophageal tumorigenesis by dietary administration of lyophilized black raspberries.	2001 Aug 15	11507061
New antioxidant and antimicrobial ellagic acid derivatives from Pteleopsis hylodendron.	2001 Jun	11458450
Constituents of Coriaria ruscifolia fruits.	2001 Jun	11429254
Quinone isomers of the WS-5995 antibiotics: synthetic antitumor agents that inhibit macromolecule synthesis, block nucleoside transport, induce DNA fragmentation, and decrease the growth and viability of L1210 leukemic cells more effectively than ellagic acid and genistein in vitro.	2001 Jun	11395569
Ellagic acid rhamnosides from the stem bark of Eucalyptus globulus.	2001 Jun	11394863
[Antioxidant properties of novel preparations--bioflavonoid derivatives and tannins].	2001 Mar-Apr	11548450
In vitro antiplasmodial activity of extracts of Tristaniopsis species and identification of the active constituents: ellagic acid and 3,4,5-trimethoxyphenyl-(6'-O-galloyl)-O-beta-D-glucopyranoside.	2001 May	11374952
Unusually large numbers of electrons for the oxidation of polyphenolic antioxidants.	2001 May 3	11325537
Evidence for a global inhibitor-induced conformation change on the Ca(2+)-ATPase of sarcoplasmic reticulum from paired inhibitor studies.	2002 Feb 26	11851435
[Studies on the chemical constituents in the leaves of Cyclocarya paliurus].	2002 Jan	12774356
Effect of ellagic acid on gastric damage induced in ischemic rat stomachs following ammonia or reperfusion.	2002 Jan 25	11848298
Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants.	2002 Mar 1	12002526
Effects of DX-9065a, an inhibitor of factor Xa, on ellagic acid-induced plantar skin thrombosis assessed in tetrodotoxin- and N(omega)-nitro-L-arginine-treated rats.	2003 Apr	12719661
Effect of naturally occurring plant phenolics on the induction of drug metabolizing enzymes by o-toluidine.	2003 Apr 15	12604171
Aldose reductase inhibitors from the nature.	2003 Aug	12871134
Phenolic content and antioxidant capacity of muscadine grapes.	2003 Aug 27	12926904
Effects of tannins on Chinese hamster cell line B14.	2003 Aug 5	12948821
Antioxidant and pro-oxidant effects of tannins in digestive cells of the freshwater mussel Unio tumidus.	2003 Aug 5	12948811
Antioxidant activity of Egyptian Eucalyptus camaldulensis var. brevirostris leaf extracts.	2003 Feb	12653437
Mechanism-based in vitro screening of potential cancer chemopreventive agents.	2003 Feb-Mar	12628514
Inhibition of metalloproteinase-9 activity and gene expression by polyphenolic compounds isolated from the bark of Tristaniopsis calobuxus (Myrtaceae).	2003 Jul	12943230
Identification of natural dyes in archeological Coptic textiles by liquid chromatography with diode array detection.	2003 Mar 14	12650256
Analysis of ellagitannins and conjugates of ellagic acid and quercetin in raspberry fruits by LC-MSn.	2003 Sep	12943785
Antioxidative capacity of extracts and constituents in Cornus capitata adventitious roots.	2003 Sep 24	13129293

Patents

Sample Use Guides

In Vivo Use Guide

The rats were fasted overnight and diabetes was induced by a single dose via intraperitoneal (i.p.) injection of streptozotocin solution (STZ). A total of 32 Wistar Albino rats was used. The rats were randomly divided into four groups, with eight rats each: normal controls (not diabetic), only ellagic acid treated (ellagic acid controls, not diabetic), diabetic control (STZ, diabetic), and ellagic acid treated diabetic (STZ + ellagic acid). The experiment was designed to last a total of 28 days. The dose of the ellagic acid was arranged (50 mg/kg/day orally)

Route of Administration: Oral

In Vitro Use Guide

A total of 2 x 106 cells were seeded in 100 mm plastic dishes and treated with 30mkM Ellagic acid . After 24 h, media was discarded and the cells were washed twice with PBS

Substance Class	Chemical Created by `admin` on `Fri Dec 16 16:49:02 UTC 2022` Edited by `admin` on `Fri Dec 16 16:49:02 UTC 2022`
Record UNII	19YRN3ZS9P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ELLAGIC ACID

Official Name

English

ELLAGIC ACID [MI]

Common Name

English

2,3,7,8-TETRAHYDROXY(1)BENZOPYRANO(5,4,3-CDE)-(1)BENZOPYRAN-5,10-DIONE

Systematic Name

English

ellagic acid [INN]

Common Name

English

ELLAGIC ACID [HSDB]

Common Name

English

NSC-407286

Code

English

NSC-656272

Code

English

Ellagic acid [WHO-DD]

Common Name

English

ELLAGIC ACID [INCI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C68538