Idronoxil
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MedKoo CAT#: 202180

CAS#: 81267-65-4

Description: 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.


Chemical Structure

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Idronoxil
CAS# 81267-65-4

Theoretical Analysis

MedKoo Cat#: 202180
Name: Idronoxil
CAS#: 81267-65-4
Chemical Formula: C15H12O3
Exact Mass: 240.08
Molecular Weight: 240.254
Elemental Analysis: C, 74.99; H, 5.03; O, 19.98

Price and Availability

Size Price Availability Quantity
5mg USD 150 Ready to ship
10mg USD 250 Ready to ship
25mg USD 550 Ready to ship
50mg USD 950 Ready to ship
100mg USD 1650 Ready to ship
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Synonym: NV-06; NV06; NV 06; Dehydroequol; Idronoxil; Phenoxodiol; Haginin E.

IUPAC/Chemical Name: 3-(4-Hydroxyphenyl)-2H-1-benzopyran-7-ol

InChi Key: ZZUBHVMHNVYXRR-UHFFFAOYSA-N

InChi Code: 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

SMILES Code: OC1=CC=C2C=C(C3=CC=C(O)C=C3)COC2=C1

Appearance: Off-white to light brown

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).

Solubility: soluble in DMSO, not soluble in water.

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: 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)    

Biological target: Phenoxodiol activates the mitochondrial caspase system, inhibits XIAP (an apoptosis inhibitor), and sensitizes the cancer cells to Fas-mediated apoptosis.
In vitro activity: Here phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle, with the resultant arrest due to the up regulation of p21WAF1. The cytotoxicity may be due to downstream signalling of molecules such as Akt and ASK1. c-Myc is a potent oncogene and expression was found to alter in PC3 cells in response to phenoxodiol. The expression of Ki-67 and Cyclin-D1 was altered after phenoxodiol treatment. Reference: Cancer Cell Int. 2014; 14: 110. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231195/
In vivo activity: Interestingly, the lower PXD (Phenoxodiol) dose (10 mg/kg) was the most effective (Fig. 4A, PXD10), as it restricted tumour size to 1.6 cm3 by day 33. The mean tumour volume measured with these animals did not increase by the end of the monitoring period (day 38), suggesting the in vivo activation of antitumour mechanisms capable of efficiently eliminating progressive cancer cell growth. Tumour growth results paralleled overall survival (Fig. 4B); 30% of mice (i.e. 3 of 10 animals) administered GEN (genistein) or PXD20 survived until day 38, whereas 40% of mice receiving 10 mg/kg PXD (PXD10) were still alive at the end of the 38-day monitoring period. Reference: J Cell Mol Med. 2009 Sep; 13(9b): 3929–3938. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516540/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 74.0 308.01
Ethanol 48.0 199.79
Water 1.0 4.16

Preparing Stock Solutions

The following data is based on the product molecular weight 240.25 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 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. PMID: 25400509; PMCID: PMC4231195. 2. 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. PMID: 19535345; PMCID: PMC2704303. 3. 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. PMID: 19220577; PMCID: PMC4516540. 4. 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. doi: 10.1002/ijc.21682. PMID: 16353157.
In vitro protocol: 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. PMID: 25400509; PMCID: PMC4231195. 2. 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. PMID: 19535345; PMCID: PMC2704303.
In vivo protocol: 1. 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. PMID: 19220577; PMCID: PMC4516540. 2. 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. doi: 10.1002/ijc.21682. PMID: 16353157.

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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.