U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C30H46O4
Molecular Weight 470.685
Optical Activity UNSPECIFIED
Defined Stereocenters 9 / 9
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENOXOLONE

SMILES

CC1(C)[C@]2([H])CC[C@]3(C)[C@]([H])(C(=O)C=C4[C@]5([H])C[C@](C)(CC[C@]5(C)CC[C@]43C)C(=O)O)[C@@]2(C)CC[C@]1([H])O

InChI

InChIKey=MPDGHEJMBKOTSU-YKLVYJNSSA-N
InChI=1S/C30H46O4/c1-25(2)21-8-11-30(7)23(28(21,5)10-9-22(25)32)20(31)16-18-19-17-27(4,24(33)34)13-12-26(19,3)14-15-29(18,30)6/h16,19,21-23,32H,8-15,17H2,1-7H3,(H,33,34)/t19-,21-,22-,23+,26+,27-,28-,29+,30+/m0/s1

HIDE SMILES / InChI
18alpha-Glycyrrhetinic acid (18-GA), a derivative of enoxolone, is used to inhibit gap junctions and furthermore, it has anti-proliferative properties against various cancer types by affecting the cell cycle proteins. 18alpha-Glycyrrhetinic acid, is a non-selective inhibitor of 11beta-hydroxysteroid dehydrogenases isozymes and results in increased whole body insulin sensitivity and decreased glucose production.

Originator

Sources: Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen Volume70B Pages 122-32 Journal 1937

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q9UBK2|||Q3LIG1
Gene ID: 10891.0
Gene Symbol: PPARGC1A
Target Organism: Homo sapiens (Human)
Target ID: P24298
Gene ID: 2875.0
Gene Symbol: GPT
Target Organism: Homo sapiens (Human)
779.0 nM [IC50]
257.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Palliative
Stronger Neo-Minophagen C

Approved Use

Chronic Hepatitis C

Launch Date

-6.943104E11
Preventing
MASO65D (Xclair®)

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
103.89 ng/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ENOXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1396.97 ng × h/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ENOXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
9.46 h
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ENOXOLONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
1500 mg single, oral
Highest studied dose
Dose: 1500 mg
Route: oral
Route: single
Dose: 1500 mg
Sources:
healthy, 29 years
n = 6
Health Status: healthy
Age Group: 29 years
Sex: M
Population Size: 6
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
major
major
minor
minor
no
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[Anti-inflammatory activity of glycyrrhizic acid derivatives].
1980 Jul-Aug
Tumorigenicity study of disodium glycyrrhizinate administered orally to mice.
1985 Nov
Therapeutic basis of glycyrrhizin on chronic hepatitis B.
1996 May
Review article: glycyrrhizin as a potential treatment for chronic hepatitis C.
1998 Mar
The enhancement of glucose uptake caused by the collapse of gap junction communication is due to an increase in astrocyte proliferation.
2001 Aug
Liquorice-induced rise in blood pressure: a linear dose-response relationship.
2001 Aug
Evidence of a role for cyclic ADP-ribose in calcium signalling and neurotransmitter release in cultured astrocytes.
2001 Aug
Enzyme-linked immunosorbent assay for glycyrrhizin using anti-glycyrrhizin monoclonal antibody and an eastern blotting technique for glucuronides of glycyrrhetic acid.
2001 Dec 15
Expression of the 11beta-hydroxysteroid dehydrogenase type II enzyme in breast tumors and modulation of activity and cell growth in PMC42 cells.
2001 Jan-Mar
'Pseudo-aldosteronism' induced by intravenous glycyrrhizin treatment of chronic hepatitis C patients.
2001 Jul
Toward prevention of hepatocellular carcinoma developing in chronic hepatitis C.
2001 Jul
Antibacterial compounds of licorice against upper airway respiratory tract pathogens.
2001 Jun
Determination of 14 chemical constituents in the traditional Chinese medicinal preparation Huangqin-Tang by high performance liquid chromatography.
2001 Jun
Potentiation of L-type calcium channels reveals nonsynaptic mechanisms that correlate spontaneous activity in the developing mammalian retina.
2001 Nov 1
Simultaneous determination of glycyrrhizin, glycyrrhetic acid and glycyrrhetic acid mono-glucuronide in Shakuyaku-kanzo-to incubated with rat feces by semi-micro high-performance liquid chromatography.
2001 Oct
Effect of pH on metabolism of glycyrrhizin, glycyrrhetic acid and glycyrrhetic acid monoglucuronide by collected human intestinal flora.
2001 Oct
An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthase-derived nitric oxide.
2001 Oct
Mechanisms of anandamide-induced vasorelaxation in rat isolated coronary arteries.
2001 Oct
An unexpected case of primary pulmonary hypertension of the neonate (PPHN). Potential role of topical administration of enoxolone.
2002
[Rhabdomyolysis and arterial hypertension caused by apparent excess of mineralocorticoids: a case report].
2002 Apr-Jun
UDP-glucuronic acid:soyasapogenol glucuronosyltransferase involved in saponin biosynthesis in germinating soybean seeds.
2002 Aug
Coordination of mesangial cell contraction by gap junction--mediated intercellular Ca(2+) wave.
2002 Aug
Cell coupling and Cx43 expression in embryonic mouse neural progenitor cells.
2002 Aug 15
Short-term cortisol infusion in the brachial artery, with and without inhibiting 11 beta-hydroxysteroid dehydrogenase, does not alter forearm vascular resistance in normotensive and hypertensive subjects.
2002 Dec
Inhibitors of gap junctions attenuate myogenic tone in cerebral arteries.
2002 Dec
Smooth muscle membrane potential modulates endothelium-dependent relaxation of rat basilar artery via myo-endothelial gap junctions.
2002 Dec 15
[Effects of glycyrrhetinic acid and IFN-alpha on HSCs collagen metabolism in rat fibrotic liver of varying stages].
2002 Feb
Induction of inducible nitric oxide synthase expression by 18beta-glycyrrhetinic acid in macrophages.
2002 Feb 27
[Quantitative determinations of glycyrrhizic acid, glycyrrhetinic acid, morphine and sodium benzoate in compound liquorice tablets by capillary zone electrophoresis].
2002 Jan
Stimulation of the BK(Ca) channel in cultured smooth muscle cells of human trachea by magnolol.
2002 Jan
Critical role of gap junctions in endothelium-dependent hyperpolarization in rat mesenteric arteries.
2002 Jul
A puzzling cause of hypokalaemia.
2002 Jul 20
Annexin 1 (lipocortin 1) mimics inhibitory effects of glucocorticoids on testosterone secretion and enhances effects of interleukin-1beta.
2002 Jun
[Effects of glycyrrhetic acid on transmitter secretion].
2002 Mar
[Licorice--not just candy].
2002 Mar 20
Gap junction intercellular communication propagates cell death in cancerous cells.
2002 Mar 27
Metabolism of constituents in Huangqin-Tang, a prescription in traditional Chinese medicine, by human intestinal flora.
2002 May
11beta-hydroxysteroid dehydrogenase type 1: a new regulator of fetal lung maturation.
2002 Oct
Modulation of renal calcium handling by 11 beta-hydroxysteroid dehydrogenase type 2.
2002 Oct
Inhibition of 3 alpha/beta,20 beta-hydroxysteroid dehydrogenase by dexamethasone, glycyrrhetinic acid and spironolactone is attenuated by deletion of 12 carboxyl-terminal residues.
2002 Sep
Hepatoprotective effects of 18beta-glycyrrhetinic acid on carbon tetrachloride-induced liver injury: inhibition of cytochrome P450 2E1 expression.
2002 Sep
Subjects with essential hypertension are more sensitive to the inhibition of 11 beta-HSD by liquorice.
2003 Feb
Biological activities of synthetic saponins and cardiac glycosides.
2003 Jan
Photoliberating inositol-1,4,5-trisphosphate triggers ATP release that is blocked by the connexin mimetic peptide gap 26.
2003 Jan
Final report on the safety assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate.
2007
Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds.
2008 Jun
Ammonium glycyrrhizinate protects gastric epithelial cells from hydrogen peroxide-induced cell death.
2009 Mar
Ammonium glycyrrhizinate-loaded niosomes as a potential nanotherapeutic system for anti-inflammatory activity in murine models.
2014
Solubilization and stabilization of macular carotenoids by water soluble oligosaccharides and polysaccharides.
2015 Apr 15
Study of an Acid-Free Technique for the Preparation of Glycyrrhetinic Acid from Ammonium Glycyrrhizinate in Subcritical Water.
2015 Nov
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: Disodium Glycyrrhizate was not carcinogenic in mice in a drinking water study at exposure levels up to 12.2 mg/kg day(-1) for 96 weeks.
Potassium Glycyrrhizinate is a skin-conditioning agent— miscellaneous in cosmetic products. Concentration of use of 1.0% was given in an industry survey.
Route of Administration: Topical
In Vitro Use Guide
Curator's Comment:: The suppressor cell activity of T6S cells was clearly counteracted by glycyrrhizin mononuclear cells (GR-MNC) in vitro in a mixed lymphocyte-tumor cell reaction. The type of cells responsible for anti-suppressor cells in GR-MNC was shown to be a CD4+ CD28+ TCR alpha/beta + Vicia villosa lectin-adherent T cell. These results suggest that GR may reverse the increased susceptibility of thermally injured mice to herpes simplex virus type 1 (HSV) infection through the induction of CD4+ contrasuppressor T cells.
Unknown
Name Type Language
ENOXOLONE
EP   INN   MART.   MI   WHO-DD  
INN  
Official Name English
ENOXOLONE [EP]
Common Name English
3.BETA.-HYDROXY-11-OXOOLEAN-12-EN-30-OIC ACID
Common Name English
ENOXOLONE [MART.]
Common Name English
ENOXOLONE [MI]
Common Name English
ENOXOLONE [EP MONOGRAPH]
Common Name English
ENOXOLONE [INN]
Common Name English
NSC-35347
Code English
GLYCYRRHETINIC ACID [INCI]
Common Name English
GLYCYRRHETINIC ACID
INCI   JAN  
INCI  
Official Name English
ENOXOLONE [WHO-DD]
Common Name English
GLYCYRRHETIC ACID
Common Name English
GLYCYRRHETINIC ACID [JAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C54678
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
DSLD 3013 (Number of products:1)
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
WHO-VATC QD03AX10
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
WHO-ATC D03AX10
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
Code System Code Type Description
FDA UNII
P540XA09DR
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
MESH
D006034
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
MERCK INDEX
M4914
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY Merck Index
INN
1794
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
PUBCHEM
10114
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
DRUG BANK
DB13089
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
DRUG CENTRAL
3178
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
CAS
471-53-4
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
ECHA (EC/EINECS)
207-444-6
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
WIKIPEDIA
GLYCYRRHETINIC ACID
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
EPA CompTox
471-53-4
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
EVMPD
SUB06543MIG
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
NCI_THESAURUS
C526
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
ChEMBL
CHEMBL230006
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY
RXCUI
1311506
Created by admin on Fri Jun 25 21:10:01 UTC 2021 , Edited by admin on Fri Jun 25 21:10:01 UTC 2021
PRIMARY RxNorm