Idronoxil (Phenoxodiol)
Idronoxil, also known as Phenoxodiol, is a synthetic flavonoid derivative. Phenoxodiol activates the mitochondrial caspase system, inhibits X-linked inhibitor of apoptosis (XIAP), and disrupts FLICE inhibitory protein (FLIP) expression, resulting in tumor cell apoptosis. This agent also inhibits DNA topoisomerase II by stabilizing the cleavable complex, thereby preventing DNA replication and resulting in tumor cell death.
1: Mahoney S, Arfuso F, Millward M, Dharmarajan A. The effects of phenoxodiol on the cell cycle of prostate cancer cell lines. Cancer Cell Int. 2014 Nov 8;14(1):110. doi: 10.1186/s12935-014-0110-z. eCollection 2014. PubMed PMID: 25400509; PubMed Central PMCID: PMC4231195.
2: Li Y, Huang X, Huang Z, Feng J. Phenoxodiol enhances the antitumor activity of gemcitabine in gallbladder cancer through suppressing Akt/mTOR pathway. Cell Biochem Biophys. 2014 Nov;70(2):1337-42. doi: 10.1007/s12013-014-0061-y. PubMed PMID: 24902539.
3: Fotopoulou C, Vergote I, Mainwaring P, Bidzinski M, Vermorken JB, Ghamande SA, Harnett P, Del Prete SA, Green JA, Spaczynski M, Blagden S, Gore M, Ledermann J, Kaye S, Gabra H. Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study. Ann Oncol. 2014 Jan;25(1):160-5. doi: 10.1093/annonc/mdt515. Epub 2013 Dec 5. PubMed PMID: 24318743.
4: Yao C, Wu S, Li D, Ding H, Wang Z, Yang Y, Yan S, Gu Z. Co-administration phenoxodiol with doxorubicin synergistically inhibit the activity of sphingosine kinase-1 (SphK1), a potential oncogene of osteosarcoma, to suppress osteosarcoma cell growth both in vivo and in vitro. Mol Oncol. 2012 Aug;6(4):392-404. doi: 10.1016/j.molonc.2012.04.002. Epub 2012 May 5. PubMed PMID: 22583777.
5: Tilley AJ, Zanatta SD, Qin CX, Kim IK, Seok YM, Stewart A, Woodman OL, Williams SJ. 2-Morpholinoisoflav-3-enes as flexible intermediates in the synthesis of phenoxodiol, isophenoxodiol, equol and analogues: vasorelaxant properties, estrogen receptor binding and Rho/RhoA kinase pathway inhibition. Bioorg Med Chem. 2012 Apr 1;20(7):2353-61. doi: 10.1016/j.bmc.2012.02.008. Epub 2012 Feb 11. PubMed PMID: 22377671.
6: Mahoney S, Arfuso F, Rogers P, Hisheh S, Brown D, Millward M, Dharmarajan A. Cytotoxic effects of the novel isoflavone, phenoxodiol, on prostate cancer cell lines. J Biosci. 2012 Mar;37(1):73-84. PubMed PMID: 22357205.
7: Wu LY, De Luca T, Watanabe T, Morré DM, Morré DJ. Metabolite modulation of HeLa cell response to ENOX2 inhibitors EGCG and phenoxodiol. Biochim Biophys Acta. 2011 Aug;1810(8):784-9. doi: 10.1016/j.bbagen.2011.04.011. Epub 2011 May 5. PubMed PMID: 21571040.
8: Kelly MG, Mor G, Husband A, O'Malley DM, Baker L, Azodi M, Schwartz PE, Rutherford TJ. Phase II evaluation of phenoxodiol in combination with cisplatin or paclitaxel in women with platinum/taxane-refractory/resistant epithelial ovarian, fallopian tube, or primary peritoneal cancers. Int J Gynecol Cancer. 2011 May;21(4):633-9. doi: 10.1097/IGC.0b013e3182126f05. PubMed PMID: 21412168.
9: Howes JB, de Souza PL, West L, Huang LJ, Howes LG. Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer. BMC Clin Pharmacol. 2011 Feb 3;11:1. doi: 10.1186/1472-6904-11-1. PubMed PMID: 21291562; PubMed Central PMCID: PMC3045896.
10: Aguero MF, Venero M, Brown DM, Smulson ME, Espinoza LA. Phenoxodiol inhibits growth of metastatic prostate cancer cells. Prostate. 2010 Aug;70(11):1211-21. doi: 10.1002/pros.21156. PubMed PMID: 20564423.
11: De Luca T, Bosneaga E, Morré DM, Morré DJ. Downstream targets of altered sphingolipid metabolism in response to inhibition of ENOX2 by phenoxodiol. Biofactors. 2008;34(3):253-60. doi: 10.3233/BIO-2009-1079. PubMed PMID: 19734127.
12: Herst PM, Davis JE, Neeson P, Berridge MV, Ritchie DS. The anti-cancer drug, phenoxodiol, kills primary myeloid and lymphoid leukemic blasts and rapidly proliferating T cells. Haematologica. 2009 Jul;94(7):928-34. doi: 10.3324/haematol.2008.003996. Epub 2009 Jun 16. PubMed PMID: 19535345; PubMed Central PMCID: PMC2704303.
13: Silasi DA, Alvero AB, Rutherford TJ, Brown D, Mor G. Phenoxodiol: pharmacology and clinical experience in cancer monotherapy and in combination with chemotherapeutic drugs. Expert Opin Pharmacother. 2009 Apr;10(6):1059-67. doi: 10.1517/14656560902837980 . Review. Erratum in: Expert Opin Pharmacother. 2009 Jun;10(8):1387. PubMed PMID: 19364253.
14: Saif MW, Tytler E, Lansigan F, Brown DM, Husband AJ. Flavonoids, phenoxodiol, and a novel agent, triphendiol, for the treatment of pancreaticobiliary cancers. Expert Opin Investig Drugs. 2009 Apr;18(4):469-79. doi: 10.1517/13543780902762835 . Review. PubMed PMID: 19278301.
15: Georgaki S, Skopeliti M, Tsiatas M, Nicolaou KA, Ioannou K, Husband A, Bamias A, Dimopoulos MA, Constantinou AI, Tsitsilonis OE. Phenoxodiol, an anticancer isoflavene, induces immunomodulatory effects in vitro and in vivo. J Cell Mol Med. 2009 Sep;13(9B):3929-38. doi: 10.1111/j.1582-4934.2009.00695.x. Epub 2009 Feb 11. PubMed PMID: 19220577; PubMed Central PMCID: PMC4516540.
16: McPherson RA, Galettis PT, de Souza PL. Enhancement of the activity of phenoxodiol by cisplatin in prostate cancer cells. Br J Cancer. 2009 Feb 24;100(4):649-55. doi: 10.1038/sj.bjc.6604920. Epub 2009 Feb 10. PubMed PMID: 19209173; PubMed Central PMCID: PMC2653737.
17: Morré DJ, McClain N, Wu LY, Kelly G, Morré DM. Phenoxodiol treatment alters the subsequent response of ENOX2 (tNOX) and growth of hela cells to paclitaxel and cisplatin. Mol Biotechnol. 2009 May;42(1):100-9. doi: 10.1007/s12033-008-9132-x. Epub 2009 Jan 21. PubMed PMID: 19156549.
18: Alvero AB, Kelly M, Rossi P, Leiser A, Brown D, Rutherford T, Mor G. Anti-tumor activity of phenoxodiol: from bench to clinic. Future Oncol. 2008 Aug;4(4):475-82. doi: 10.2217/14796694.4.4.475. Review. PubMed PMID: 18684059.
19: Herst PM, Petersen T, Jerram P, Baty J, Berridge MV. The antiproliferative effects of phenoxodiol are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells. Biochem Pharmacol. 2007 Dec 3;74(11):1587-95. Epub 2007 Aug 19. PubMed PMID: 17904534.
20: Klein R, Brown D, Turnley AM. Phenoxodiol protects against Cisplatin induced neurite toxicity in a PC-12 cell model. BMC Neurosci. 2007 Aug 1;8:61. PubMed PMID: 17672914; PubMed Central PMCID: PMC1950519.
2: Li Y, Huang X, Huang Z, Feng J. Phenoxodiol enhances the antitumor activity of gemcitabine in gallbladder cancer through suppressing Akt/mTOR pathway. Cell Biochem Biophys. 2014 Nov;70(2):1337-42. doi: 10.1007/s12013-014-0061-y. PubMed PMID: 24902539.
3: Fotopoulou C, Vergote I, Mainwaring P, Bidzinski M, Vermorken JB, Ghamande SA, Harnett P, Del Prete SA, Green JA, Spaczynski M, Blagden S, Gore M, Ledermann J, Kaye S, Gabra H. Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study. Ann Oncol. 2014 Jan;25(1):160-5. doi: 10.1093/annonc/mdt515. Epub 2013 Dec 5. PubMed PMID: 24318743.
4: Yao C, Wu S, Li D, Ding H, Wang Z, Yang Y, Yan S, Gu Z. Co-administration phenoxodiol with doxorubicin synergistically inhibit the activity of sphingosine kinase-1 (SphK1), a potential oncogene of osteosarcoma, to suppress osteosarcoma cell growth both in vivo and in vitro. Mol Oncol. 2012 Aug;6(4):392-404. doi: 10.1016/j.molonc.2012.04.002. Epub 2012 May 5. PubMed PMID: 22583777.
5: Tilley AJ, Zanatta SD, Qin CX, Kim IK, Seok YM, Stewart A, Woodman OL, Williams SJ. 2-Morpholinoisoflav-3-enes as flexible intermediates in the synthesis of phenoxodiol, isophenoxodiol, equol and analogues: vasorelaxant properties, estrogen receptor binding and Rho/RhoA kinase pathway inhibition. Bioorg Med Chem. 2012 Apr 1;20(7):2353-61. doi: 10.1016/j.bmc.2012.02.008. Epub 2012 Feb 11. PubMed PMID: 22377671.
6: Mahoney S, Arfuso F, Rogers P, Hisheh S, Brown D, Millward M, Dharmarajan A. Cytotoxic effects of the novel isoflavone, phenoxodiol, on prostate cancer cell lines. J Biosci. 2012 Mar;37(1):73-84. PubMed PMID: 22357205.
7: Wu LY, De Luca T, Watanabe T, Morré DM, Morré DJ. Metabolite modulation of HeLa cell response to ENOX2 inhibitors EGCG and phenoxodiol. Biochim Biophys Acta. 2011 Aug;1810(8):784-9. doi: 10.1016/j.bbagen.2011.04.011. Epub 2011 May 5. PubMed PMID: 21571040.
8: Kelly MG, Mor G, Husband A, O'Malley DM, Baker L, Azodi M, Schwartz PE, Rutherford TJ. Phase II evaluation of phenoxodiol in combination with cisplatin or paclitaxel in women with platinum/taxane-refractory/resistant epithelial ovarian, fallopian tube, or primary peritoneal cancers. Int J Gynecol Cancer. 2011 May;21(4):633-9. doi: 10.1097/IGC.0b013e3182126f05. PubMed PMID: 21412168.
9: Howes JB, de Souza PL, West L, Huang LJ, Howes LG. Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer. BMC Clin Pharmacol. 2011 Feb 3;11:1. doi: 10.1186/1472-6904-11-1. PubMed PMID: 21291562; PubMed Central PMCID: PMC3045896.
10: Aguero MF, Venero M, Brown DM, Smulson ME, Espinoza LA. Phenoxodiol inhibits growth of metastatic prostate cancer cells. Prostate. 2010 Aug;70(11):1211-21. doi: 10.1002/pros.21156. PubMed PMID: 20564423.
11: De Luca T, Bosneaga E, Morré DM, Morré DJ. Downstream targets of altered sphingolipid metabolism in response to inhibition of ENOX2 by phenoxodiol. Biofactors. 2008;34(3):253-60. doi: 10.3233/BIO-2009-1079. PubMed PMID: 19734127.
12: Herst PM, Davis JE, Neeson P, Berridge MV, Ritchie DS. The anti-cancer drug, phenoxodiol, kills primary myeloid and lymphoid leukemic blasts and rapidly proliferating T cells. Haematologica. 2009 Jul;94(7):928-34. doi: 10.3324/haematol.2008.003996. Epub 2009 Jun 16. PubMed PMID: 19535345; PubMed Central PMCID: PMC2704303.
13: Silasi DA, Alvero AB, Rutherford TJ, Brown D, Mor G. Phenoxodiol: pharmacology and clinical experience in cancer monotherapy and in combination with chemotherapeutic drugs. Expert Opin Pharmacother. 2009 Apr;10(6):1059-67. doi: 10.1517/14656560902837980 . Review. Erratum in: Expert Opin Pharmacother. 2009 Jun;10(8):1387. PubMed PMID: 19364253.
14: Saif MW, Tytler E, Lansigan F, Brown DM, Husband AJ. Flavonoids, phenoxodiol, and a novel agent, triphendiol, for the treatment of pancreaticobiliary cancers. Expert Opin Investig Drugs. 2009 Apr;18(4):469-79. doi: 10.1517/13543780902762835 . Review. PubMed PMID: 19278301.
15: Georgaki S, Skopeliti M, Tsiatas M, Nicolaou KA, Ioannou K, Husband A, Bamias A, Dimopoulos MA, Constantinou AI, Tsitsilonis OE. Phenoxodiol, an anticancer isoflavene, induces immunomodulatory effects in vitro and in vivo. J Cell Mol Med. 2009 Sep;13(9B):3929-38. doi: 10.1111/j.1582-4934.2009.00695.x. Epub 2009 Feb 11. PubMed PMID: 19220577; PubMed Central PMCID: PMC4516540.
16: McPherson RA, Galettis PT, de Souza PL. Enhancement of the activity of phenoxodiol by cisplatin in prostate cancer cells. Br J Cancer. 2009 Feb 24;100(4):649-55. doi: 10.1038/sj.bjc.6604920. Epub 2009 Feb 10. PubMed PMID: 19209173; PubMed Central PMCID: PMC2653737.
17: Morré DJ, McClain N, Wu LY, Kelly G, Morré DM. Phenoxodiol treatment alters the subsequent response of ENOX2 (tNOX) and growth of hela cells to paclitaxel and cisplatin. Mol Biotechnol. 2009 May;42(1):100-9. doi: 10.1007/s12033-008-9132-x. Epub 2009 Jan 21. PubMed PMID: 19156549.
18: Alvero AB, Kelly M, Rossi P, Leiser A, Brown D, Rutherford T, Mor G. Anti-tumor activity of phenoxodiol: from bench to clinic. Future Oncol. 2008 Aug;4(4):475-82. doi: 10.2217/14796694.4.4.475. Review. PubMed PMID: 18684059.
19: Herst PM, Petersen T, Jerram P, Baty J, Berridge MV. The antiproliferative effects of phenoxodiol are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells. Biochem Pharmacol. 2007 Dec 3;74(11):1587-95. Epub 2007 Aug 19. PubMed PMID: 17904534.
20: Klein R, Brown D, Turnley AM. Phenoxodiol protects against Cisplatin induced neurite toxicity in a PC-12 cell model. BMC Neurosci. 2007 Aug 1;8:61. PubMed PMID: 17672914; PubMed Central PMCID: PMC1950519.
| Chemical | |
|---|---|
| CAS Num | 81267-65-4 |
| Chemical Formula | C15H12O3 |
| Molecular Weight | 240.25398 |
| IUPAC Chemical Name | 3-(4-Hydroxyphenyl)-2H-1-benzopyran-7-ol |
| Exact Mass | 240.07864 |
| Elemental Analysis | C, 74.99; H, 5.03; O, 19.98 |
| Synonym | NV-06; NV06; NV 06; Dehydroequol. Idronoxil; Phenoxodiol; Haginin E. |
| Solubility | soluble in DMSO, not soluble in water. |
| SMILES Code | OC1=CC=C2C=C(C3=CC=C(O)C=C3)COC2=C1 |
| Biological | |
| Targets and Effects | topoisomerase II inhibitor |
| Pathways | Apoptosis |
| Physical | |
| Appearance | solid powder |
| Purity | >98% (or refer to the Certificate of Analysis) |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| Storage Condition | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Shelf Life | >5 years if stored properly |
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