Back to products

Browse products

MedKoo product information:

Idronoxil (Phenoxodiol)

Description of Idronoxil (Phenoxodiol): 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. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:   Yale University; Marshall Edwards; and Novogen, Inc. (http://www.novogen.com).

The primary target of phenoxodiol is a protein receptor known as tNOX (NADH oxidase). This receptor plays an important role in helping to maintain high levels of anti-apoptotic proteins in the cancer cell. By binding to the tNOX receptor and blocking its function, phenoxodiol eventually switches off the production of the anti-apoptotic proteins. This in turn leads to activation of proteolytic enzymes within the cancer cell known as caspases. These digest the cancer cell when activated, leading to the self-destructive form of cell death known as apoptosis. (from Marshall Edwards Inc's website)

 1: Aguero MF, Venero M, Brown DM, Smulson ME, Espinoza LA. Phenoxodiol inhibits growth of metastatic prostate cancer cells. Prostate. 2010 Mar 30;70(11):1211-1221. [Epub ahead of print] PubMed PMID: 20564423.

2: De Luca T, Morré DM, Morré DJ. Reciprocal relationship between cytosolic NADH and ENOX2 inhibition triggers sphingolipid-induced apoptosis in HeLa cells. J Cell Biochem. 2010 Aug 15;110(6):1504-11. PubMed PMID: 20518072.

3: De Luca T, Bosneaga E, Morré DM, Morré DJ. Downstream targets of altered sphingolipid metabolism in response to inhibition of ENOX2 by phenoxodiol. Biofactors. 2009;34(3):253-60. PubMed PMID: 19734127.

4: 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. Epub 2009 Jun 16. PubMed PMID: 19535345; PubMed Central PMCID: PMC2704303.

5: 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. Review. Erratum in: Expert Opin Pharmacother. 2009 Jun;10(8):1387. PubMed PMID: 19364253.

6: 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. Review. PubMed PMID: 19278301.

7: 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. Epub 2009 Feb 11. PubMed PMID: 19220577.

8: 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. Epub 2009 Feb 10. PubMed PMID: 19209173; PubMed Central PMCID: PMC2653737.

9: 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. Epub 2009 Jan 21. PubMed PMID: 19156549.

10: 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. Review. PubMed PMID: 18684059.

11: Mor G, Montagna MK, Alvero AB. Modulation of apoptosis to reverse chemoresistance. Methods Mol Biol. 2008;414:1-12. Review. PubMed PMID: 18175807.

12: 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.

13: 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.

14: Morré DJ, Chueh PJ, Yagiz K, Balicki A, Kim C, Morré DM. ECTO-NOX target for the anticancer isoflavene phenoxodiol. Oncol Res. 2007;16(7):299-312. PubMed PMID: 17518268.

15: Alvero AB, Brown D, Montagna M, Matthews M, Mor G. Phenoxodiol-Topotecan co-administration exhibit significant anti-tumor activity without major adverse side effects. Cancer Biol Ther. 2007 Apr;6(4):612-7. PubMed PMID: 17457041.

16: Kluger HM, McCarthy MM, Alvero AB, Sznol M, Ariyan S, Camp RL, Rimm DL, Mor G. The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization. J Transl Med. 2007 Jan 26;5:6. PubMed PMID: 17257402; PubMed Central PMCID: PMC1796544.

17: Yagiz K, Wu LY, Kuntz CP, James Morré D, Morré DM. Mouse embryonic fibroblast cells from transgenic mice overexpressing tNOX exhibit an altered growth and drug response phenotype. J Cell Biochem. 2007 May 15;101(2):295-306. PubMed PMID: 17115410.

18: Yu F, Watts RN, Zhang XD, Borrow JM, Hersey P. Involvement of BH3-only proapoptotic proteins in mitochondrial-dependent Phenoxodiol-induced apoptosis of human melanoma cells. Anticancer Drugs. 2006 Nov;17(10):1151-61. PubMed PMID: 17075314.

19: De Luca T, Morré DM, Zhao H, Morré DJ. NAD+/NADH and/or CoQ/CoQH2 ratios from plasma membrane electron transport may determine ceramide and sphingosine-1-phosphate levels accompanying G1 arrest and apoptosis. Biofactors. 2005;25(1-4):43-60. PubMed PMID: 16873929.

20: Davies SL, Bozzo J. Spotlight on tNOX: a tumor-selective target for cancer therapies. Drug News Perspect. 2006 May;19(4):223-5. Review. PubMed PMID: 16823496.

21: Mor G, Fu HH, Alvero AB. Phenoxodiol, a novel approach for the treatment of ovarian cancer. Curr Opin Investig Drugs. 2006 Jun;7(6):542-8. Review. PubMed PMID: 16784025.

22: Choueiri TK, Mekhail T, Hutson TE, Ganapathi R, Kelly GE, Bukowski RM. Phase I trial of phenoxodiol delivered by continuous intravenous infusion in patients with solid cancer. Ann Oncol. 2006 May;17(5):860-5. Epub 2006 Mar 8. PubMed PMID: 16524966.

23: Choueiri TK, Wesolowski R, Mekhail TM. Phenoxodiol: isoflavone analog with antineoplastic activity. Curr Oncol Rep. 2006 Mar;8(2):104-7. Review. PubMed PMID: 16507219.

24: de Souza PL, Liauw W, Links M, Pirabhahar S, Kelly G, Howes LG. Phase I and pharmacokinetic study of weekly NV06 (Phenoxodiol), a novel isoflav-3-ene, in patients with advanced cancer. Cancer Chemother Pharmacol. 2006 Oct;58(4):427-33. Epub 2006 Feb 4. PubMed PMID: 16463060.

25: Alvero AB, O'Malley D, Brown D, Kelly G, Garg M, Chen W, Rutherford T, Mor G. Molecular mechanism of phenoxodiol-induced apoptosis in ovarian carcinoma cells. Cancer. 2006 Feb 1;106(3):599-608. PubMed PMID: 16388521.

26: Gamble JR, Xia P, Hahn CN, Drew JJ, Drogemuller CJ, Brown D, Vadas MA. Phenoxodiol, an experimental anticancer drug, shows potent antiangiogenic properties in addition to its antitumour effects. Int J Cancer. 2006 May 15;118(10):2412-20. PubMed PMID: 16353157.

27: Brown DM, Kelly GE, Husband AJ. Flavonoid compounds in maintenance of prostate health and prevention and treatment of cancer. Mol Biotechnol. 2005 Jul;30(3):253-70. Review. PubMed PMID: 15988050.

28: Axanova L, Morré DJ, Morré DM. Growth of LNCaP cells in monoculture and coculture with osteoblasts and response to tNOX inhibitors. Cancer Lett. 2005 Jul 8;225(1):35-40. Epub 2004 Dec 24. PubMed PMID: 15922855.

29: Aguero MF, Facchinetti MM, Sheleg Z, Senderowicz AM. Phenoxodiol, a novel isoflavone, induces G1 arrest by specific loss in cyclin-dependent kinase 2 activity by p53-independent induction of p21WAF1/CIP1. Cancer Res. 2005 Apr 15;65(8):3364-73. PubMed PMID: 15833870.

30: Sapi E, Alvero AB, Chen W, O'Malley D, Hao XY, Dwipoyono B, Garg M, Kamsteeg M, Rutherford T, Mor G. Resistance of ovarian carcinoma cells to docetaxel is XIAP dependent and reversible by phenoxodiol. Oncol Res. 2004;14(11-12):567-78. PubMed PMID: 15666998.

31: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Sep;26(7):587-612. Review. PubMed PMID: 15538546.

32: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Jul-Aug;26(6):473-503. PubMed PMID: 15349141.

33: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Apr;26(3):211-44. PubMed PMID: 15148527.

34: Wilkinson E. Phenoxodiol offers hope for ovarian cancer. Lancet Oncol. 2004 Apr;5(4):201. PubMed PMID: 15085844.

35: Straszewski-Chavez SL, Abrahams VM, Funai EF, Mor G. X-linked inhibitor of apoptosis (XIAP) confers human trophoblast cell resistance to Fas-mediated apoptosis. Mol Hum Reprod. 2004 Jan;10(1):33-41. PubMed PMID: 14665704.

36: Kamsteeg M, Rutherford T, Sapi E, Hanczaruk B, Shahabi S, Flick M, Brown D, Mor G. Phenoxodiol--an isoflavone analog--induces apoptosis in chemoresistant ovarian cancer cells. Oncogene. 2003 May 1;22(17):2611-20. PubMed PMID: 12730675.

37: Kelly GE, Husband AJ. Flavonoid compounds in the prevention and treatment of prostate cancer. Methods Mol Med. 2003;81:377-94. Review. PubMed PMID: 12725132.

38: Constantinou AI, Mehta R, Husband A. Phenoxodiol, a novel isoflavone derivative, inhibits dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats. Eur J Cancer. 2003 May;39(7):1012-8. PubMed PMID: 12706372.

39: Constantinou AI, Husband A. Phenoxodiol (2H-1-benzopyran-7-0,1,3-(4-hydroxyphenyl)), a novel isoflavone derivative, inhibits DNA topoisomerase II by stabilizing the cleavable complex. Anticancer Res. 2002 Sep-Oct;22(5):2581-5. PubMed PMID: 12529967.