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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

Description

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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
660.69 nM [IC50]
32.0 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
17.5 μg/mL
5 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
29.4 μg/mL
10 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
42.9 μg/mL
15 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
46.7 μg/mL
20 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
59.5 μg/mL
25 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
88.7 μg/mL
30 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
1514.27 ng/mL
0.65 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
3881.5 ng/mL
1.3 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
5276.93 ng/mL
2.2 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
5729.23 ng/mL
3.3 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
33504.35 ng/mL
20 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
60017.8 ng/mL
27 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
7218 μg × min/mL
5 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
11316 μg × min/mL
10 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
16266 μg × min/mL
15 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
21450 μg × min/mL
20 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
15256 μg × min/mL
25 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
23039 μg × min/mL
30 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
233.86 μg × min/mL
0.65 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
711.33 μg × min/mL
1.3 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
1028.69 μg × min/mL
2.2 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
965.13 μg × min/mL
3.3 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
5885.62 μg × min/mL
20 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
10516.25 μg × min/mL
27 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
313 min
5 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
366 min
10 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
317 min
15 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
419 min
20 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
254 min
25 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
156 min
30 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens
4.8 h
0.65 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
24 h
1.3 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
16.8 h
2.2 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
8 h
3.3 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
8 h
20 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens
4.8 h
27 mg/kg 1 times / day multiple, intravenous
IDRONOXIL plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
0.01%
5 mg/kg 1 times / week multiple, intravenous
IDRONOXIL plasma
Homo sapiens

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
400mg phenoxodiol three times daily in 28 day cycles.
Route of Administration: Oral
In Vitro Use Guide
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.