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

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Status:
Investigational
Source:
NCT00382811: Phase 3 Interventional Completed Fallopian Tube Cancer
(2006)
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)



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.