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
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
| 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 |
DescriptionCurator'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
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.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2724 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22377671 |
660.69 nM [IC50] | ||
Target ID: GO:0030965 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17904534 |
32.0 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
17.5 μg/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
5 mg/kg 1 times / week multiple, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
29.4 μg/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
10 mg/kg 1 times / week multiple, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
42.9 μg/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
15 mg/kg 1 times / week multiple, intravenous dose: 15 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
46.7 μg/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
20 mg/kg 1 times / week multiple, intravenous dose: 20 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
59.5 μg/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
25 mg/kg 1 times / week multiple, intravenous dose: 25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
88.7 μg/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
30 mg/kg 1 times / week multiple, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1514.27 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
0.65 mg/kg 1 times / day multiple, intravenous dose: 0.65 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3881.5 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
1.3 mg/kg 1 times / day multiple, intravenous dose: 1.3 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
5276.93 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
2.2 mg/kg 1 times / day multiple, intravenous dose: 2.2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
5729.23 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
3.3 mg/kg 1 times / day multiple, intravenous dose: 3.3 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
33504.35 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
20 mg/kg 1 times / day multiple, intravenous dose: 20 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
60017.8 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
27 mg/kg 1 times / day multiple, intravenous dose: 27 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
7218 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
5 mg/kg 1 times / week multiple, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
11316 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
10 mg/kg 1 times / week multiple, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
16266 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
15 mg/kg 1 times / week multiple, intravenous dose: 15 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
21450 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
20 mg/kg 1 times / week multiple, intravenous dose: 20 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
15256 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
25 mg/kg 1 times / week multiple, intravenous dose: 25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
23039 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
30 mg/kg 1 times / week multiple, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
233.86 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
0.65 mg/kg 1 times / day multiple, intravenous dose: 0.65 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
711.33 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
1.3 mg/kg 1 times / day multiple, intravenous dose: 1.3 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1028.69 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
2.2 mg/kg 1 times / day multiple, intravenous dose: 2.2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
965.13 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
3.3 mg/kg 1 times / day multiple, intravenous dose: 3.3 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
5885.62 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
20 mg/kg 1 times / day multiple, intravenous dose: 20 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
10516.25 μg × min/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
27 mg/kg 1 times / day multiple, intravenous dose: 27 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
313 min CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
5 mg/kg 1 times / week multiple, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
366 min CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
10 mg/kg 1 times / week multiple, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
317 min CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
15 mg/kg 1 times / week multiple, intravenous dose: 15 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
419 min CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
20 mg/kg 1 times / week multiple, intravenous dose: 20 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
254 min CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
25 mg/kg 1 times / week multiple, intravenous dose: 25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
156 min CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
30 mg/kg 1 times / week multiple, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
4.8 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
0.65 mg/kg 1 times / day multiple, intravenous dose: 0.65 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
24 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
1.3 mg/kg 1 times / day multiple, intravenous dose: 1.3 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
16.8 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
2.2 mg/kg 1 times / day multiple, intravenous dose: 2.2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
8 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
3.3 mg/kg 1 times / day multiple, intravenous dose: 3.3 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
8 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
20 mg/kg 1 times / day multiple, intravenous dose: 20 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
4.8 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16524966/ |
27 mg/kg 1 times / day multiple, intravenous dose: 27 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.01% CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/16463060/ |
5 mg/kg 1 times / week multiple, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IDRONOXIL plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Reciprocal relationship between cytosolic NADH and ENOX2 inhibition triggers sphingolipid-induced apoptosis in HeLa cells. | 2010-08-15 |
|
| The antiproliferative effects of phenoxodiol are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells. | 2007-12-03 |
|
| Phenoxodiol protects against Cisplatin induced neurite toxicity in a PC-12 cell model. | 2007-08-01 |
|
| Phenoxodiol, a novel approach for the treatment of ovarian cancer. | 2006-06 |
|
| Phenoxodiol: isoflavone analog with antineoplastic activity. | 2006-03 |
|
| Molecular mechanism of phenoxodiol-induced apoptosis in ovarian carcinoma cells. | 2006-02-01 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00382811
400mg phenoxodiol three times daily in 28 day cycles.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17904534
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
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admin
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Edited
Mon Mar 31 17:58:29 GMT 2025
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on
Mon Mar 31 17:58:29 GMT 2025
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| Record UNII |
995FT1W541
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Validated (UNII)
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NCI_THESAURUS |
C1968
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FDA ORPHAN DRUG |
868622
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FDA ORPHAN DRUG |
252307
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FDA ORPHAN DRUG |
254407
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FDA ORPHAN DRUG |
251707
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995FT1W541
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CHEMBL1957038
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DB04915
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m4146
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SUB27079
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100000090499
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C471183
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C2642
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