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
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
Cmax
AUC
T1/2
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
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Drug as perpetrator
Sourcing
PubMed
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.