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Details

Stereochemistry ACHIRAL
Molecular Formula C15H12O3
Molecular Weight 240.254
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IDRONOXIL

SMILES

OC1=CC=C(C=C1)C2=CC3=CC=C(O)C=C3OC2

InChI

InChIKey=ZZUBHVMHNVYXRR-UHFFFAOYSA-N
InChI=1S/C15H12O3/c16-13-4-1-10(2-5-13)12-7-11-3-6-14(17)8-15(11)18-9-12/h1-8,16-17H,9H2

HIDE SMILES / InChI

Molecular Formula C15H12O3
Molecular Weight 240.254
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00382811 | https://www.ncbi.nlm.nih.gov/pubmed/17904534 | https://clinicaltrials.gov/ct2/show/NCT03041285 | https://www.ncbi.nlm.nih.gov/pubmed/22377671 | https://clinicaltrials.gov/ct2/show/NCT00091377 | https://clinicaltrials.gov/ct2/show/NCT00303888

Idronoxil (Phenoxodiol) is a synthetic flavonoid derivative developed by MEI Pharma for cancer treatment. Idronoxil inhibits proliferation of many cancer cell lines and induces apoptosis by disrupting FLICE-inhibitory protein, FLIP, expression and by caspase-dependent and -independent degradation of the X-linked inhibitor of apoptosis, XIAP. In addition, Idronoxil sensitizes drug-resistant tumour cells to anticancer drugs including paclitaxel, carboplatin, and gemcitabine. The antiproliferative effects of Idronoxil are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells. Idronoxil displays anti-cancer activity against all forms of cancer tested in vitro and in vivo to date, using cells representative of all major forms of cancer. While having a modest ability to kill cancer cells(IC50 range between about 1-5 uM), preclinical studies point to its optimal use being to sensitize cancer cells to the toxic effects of standard therapies (chemotherapy and radiotherapy). The rationale is that a sub-lethal inhibitory effect on sphingosine kinase activity reduces the ability of the cancer cell to operate drug-resistance mechanisms and to effect repair of drug- or radiation-induced damage to DNA. In the case of cytotoxic drugs such as cisplatin, carboplatin, paclitaxel, Doxorubicin, and gemcitabine, Idronoxil is an exquisite sensitizer, increasing the cytotoxic potential of those agents by between 103 -105 times, in the process restoring sensitivity to cancer cells highly refractory to those agents.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
660.69 nM [IC50]
32.0 µM [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
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 9.3495 uM]
PubMed

PubMed

TitleDatePubMed
Phenoxodiol, a novel approach for the treatment of ovarian cancer.
2006 Jun
The antiproliferative effects of phenoxodiol are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells.
2007 Dec 3
Reciprocal relationship between cytosolic NADH and ENOX2 inhibition triggers sphingolipid-induced apoptosis in HeLa cells.
2010 Aug 15
Patents

Patents

Sample Use Guides

400mg phenoxodiol three times daily in 28 day cycles.
Route of Administration: Oral
HL60 and HL60ro cells were grown to mid-exponential phase in RPMI-1640, centrifuged at 130 x g at room temperature for 5 min and resuspended in 10 mL of fresh medium in the absence and presence of phenoxodiol and/or doxorubicin to a density of 2 x 10^5 cells/mL. Viable cells, as determined by Trypan blue exclusion, were counted in a Neubauer haemocytometer every 24 h for several days.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:28:47 GMT 2023
Edited
by admin
on Fri Dec 15 15:28:47 GMT 2023
Record UNII
995FT1W541
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
IDRONOXIL
INN   USAN  
USAN   INN  
Official Name English
(±)-CIS-3-(4-HYDROXYPHENYL)-4-(4-METHOXYPHENYL)-3,4-DIHYDRO-2H-CROMEN-7-OL
Systematic Name English
IDRONOXIL COMPONENT OF NOX66 SUPPOSITORY
Common Name English
NOX-66 COMPONENT IDRONOXIL
Common Name English
Idronoxil [WHO-DD]
Common Name English
IDRONOXIL [USAN]
Common Name English
DEHYDROEQUOL [MI]
Common Name English
3-(4-Hydroxyphenyl)-2H-chromen-7-ol
Systematic Name English
idronoxil [INN]
Common Name English
NV-06
Code English
PHENOXODIOL
Common Name English
NOX66 SUPPOSITORY COMPONENT IDRONOXIL
Common Name English
2H-1-BENZOPYRAN-7-OL, 3-(4-HYDROXYPHENYL)-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1968
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
FDA ORPHAN DRUG 868622
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
FDA ORPHAN DRUG 252307
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
FDA ORPHAN DRUG 254407
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
FDA ORPHAN DRUG 251707
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
Code System Code Type Description
USAN
NN-61
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
FDA UNII
995FT1W541
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
ChEMBL
CHEMBL1957038
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
DRUG BANK
DB04915
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
CAS
81267-65-4
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
EPA CompTox
DTXSID50231029
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
INN
8354
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
PUBCHEM
219100
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
MERCK INDEX
m4146
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY Merck Index
EVMPD
SUB27079
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
SMS_ID
100000090499
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
MESH
C471183
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
NCI_THESAURUS
C2642
Created by admin on Fri Dec 15 15:28:47 GMT 2023 , Edited by admin on Fri Dec 15 15:28:47 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY