Idoxifene

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 205880

CAS#: 116057-75-1

Description: Idoxifene is a non-steroidal estrogen antagonist. It is also structurally analogous to tamoxifen. Idoxifene was both active and well tolerated in postmenopausal women with metastatic breast cancer. Idoxifene had similar efficacy and toxicity to tamoxifen in this randomized comparison. (source: Ann Oncol. 2003 Feb;14(2):233-41).


Price and Availability

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Price

1g
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Size
Price

2g
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Size
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5g
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Idoxifene is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 205880
Name: Idoxifene
CAS#: 116057-75-1
Chemical Formula: C28H30INO
Exact Mass: 523.13721
Molecular Weight: 523.44837
Elemental Analysis: C, 64.25; H, 5.78; I, 24.24; N, 2.68; O, 3.06


Synonym:

IUPAC/Chemical Name: (E)-1-(2-(4-(1-(4-Iodophenyl)-2-phenylbut-1-en-1-yl)phenoxy)ethyl)pyrrolidine

InChi Key: JJKOTMDDZAJTGQ-DQSJHHFOSA-N

InChi Code: InChI=1S/C28H30INO/c1-2-27(22-8-4-3-5-9-22)28(23-10-14-25(29)15-11-23)24-12-16-26(17-13-24)31-21-20-30-18-6-7-19-30/h3-5,8-17H,2,6-7,18-21H2,1H3/b28-27-

SMILES Code: CC/C(C1=CC=CC=C1)=C(C2=CC=C(OCCN3CCCC3)C=C2)\C4=CC=C(I)C=C4


Technical Data

Appearance:
Solid powder

Purity:
>98%

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 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).

Harmonized System Code:
293490


Additional Information

According to news released in 1999, After consultation with the US Food and Drug Administration, SmithKlineBeecham has opted to abandon development of its selective estrogen receptor modulator idoxifene for the prevention of osteoporosis due to the high incidence of side effects. However, assessment of the drug for the treatment of breast cancer is to continue. Despite peak sales forecasts by analysts of L700 million ($1.13 billion) for idoxifene, SB remained upbeat about its profit potential this year  (source: thepharmaletter.com).  
 
 
 


References

1: Rehm S, Solleveld HA, Portelli ST, Wier PJ. Histologic changes in ovary, uterus, vagina, and mammary gland of mature beagle dogs treated with the SERM idoxifene. Birth Defects Res B Dev Reprod Toxicol. 2007 Jun;80(3):225-32. PubMed PMID: 17570126.

2: Zhou YJ, Yin DM, Chen HS, Shi JH, Sha BX, Wang X. Inhibitory effects of idoxifene on hepatic fibrosis in rats. Acta Pharmacol Sin. 2005 May;26(5):581-6. PubMed PMID: 15842777.

3: Wei GZ, Yu J, Zhu YL, Lin SX, Kang YF, Wang R, Zhou JJ, Zhang QH. [Vasorelaxing effect of idoxifene on human internal mammary arteries]. Sheng Li Xue Bao. 2004 Feb 25;56(1):16-20. Chinese. PubMed PMID: 14985823.

4: Johnston SR, Gumbrell LA, Evans TR, Coleman RE, Smith IE, Twelves CJ, Soukop M, Rea DW, Earl HM, Howell A, Jones A, Canney P, Powles TJ, Haynes BP, Nutley B, Grimshaw R, Jarman M, Halbert GW, Brampton M, Haviland J, Dowsett M, Coombes RC; Cancer Research UK Phase I/II Committee. A cancer research (UK) randomized phase II study of idoxifene in patients with locally advanced/metastatic breast cancer resistant to tamoxifen. Cancer Chemother Pharmacol. 2004 Apr;53(4):341-8. Epub 2004 Jan 13. PubMed PMID: 14722733.

5: Lu G, Shimizu I, Cui X, Itonaga M, Tamaki K, Fukuno H, Inoue H, Honda H, Ito S. Antioxidant and antiapoptotic activities of idoxifene and estradiol in hepatic fibrosis in rats. Life Sci. 2004 Jan 2;74(7):897-907. PubMed PMID: 14659978.

6: Inoue H, Shimizu I, Lu G, Itonaga M, Cui X, Okamura Y, Shono M, Honda H, Inoue S, Muramatsu M, Ito S. Idoxifene and estradiol enhance antiapoptotic activity through estrogen receptor-beta in cultured rat hepatocytes. Dig Dis Sci. 2003 Mar;48(3):570-80. PubMed PMID: 12757172.

7: Arpino G, Nair Krishnan M, Doval Dinesh C, Bardou VJ, Clark GM, Elledge RM. Idoxifene versus tamoxifen: a randomized comparison in postmenopausal patients with metastatic breast cancer. Ann Oncol. 2003 Feb;14(2):233-41. PubMed PMID: 12562650.

8: Yang C, Henion J. Atmospheric pressure photoionization liquid chromatographic-mass spectrometric determination of idoxifene and its metabolites in human plasma. J Chromatogr A. 2002 Sep 13;970(1-2):155-65. PubMed PMID: 12350090.

9: Christopher TA, Lopez BL, Stillwagon JC, Gao F, Gao E, Ma XL, Ohlstein EH, Yue TL. Idoxifene causes endothelium-dependent, nitric oxide-mediated vasorelaxation in male rats. Eur J Pharmacol. 2002 Jun 20;446(1-3):139-43. PubMed PMID: 12098595.

10: Gutman M, Couillard S, Roy J, Labrie F, Candas B, Labrie C. Comparison of the effects of EM-652 (SCH57068), tamoxifen, toremifene, droloxifene, idoxifene, GW-5638 and raloxifene on the growth of human ZR-75-1 breast tumors in nude mice. Int J Cancer. 2002 May 10;99(2):273-8. PubMed PMID: 11979444.

11: van Rietbergen B, Majumdar S, Newitt D, MacDonald B. High-resolution MRI and micro-FE for the evaluation of changes in bone mechanical properties during longitudinal clinical trials: application to calcaneal bone in postmenopausal women after one year of idoxifene treatment. Clin Biomech (Bristol, Avon). 2002 Feb;17(2):81-8. PubMed PMID: 11832257.

12: Bäumer AT, Wassmann S, Ahlbory K, Strehlow K, Müller C, Sauer H, Böhm M, Nickenig G. Reduction of oxidative stress and AT1 receptor expression by the selective oestrogen receptor modulator idoxifene. Br J Pharmacol. 2001 Oct;134(3):579-84. PubMed PMID: 11588112; PubMed Central PMCID: PMC1572993.

13: Omoya T, Shimizu I, Zhou Y, Okamura Y, Inoue H, Lu G, Itonaga M, Honda H, Nomura M, Ito S. Effects of idoxifene and estradiol on NF-kappaB activation in cultured rat hepatocytes undergoing oxidative stress. Liver. 2001 Jun;21(3):183-91. PubMed PMID: 11422781.

14: Zhang H, Henion J. Comparison between liquid chromatography-time of-flight mass spectrometry and selected reaction monitoring liquid chromatography-mass spectrometry for quantitative determination of idoxifene in human plasma. J Chromatogr B Biomed Sci Appl. 2001 Jun 5;757(1):151-9. PubMed PMID: 11419740.

15: Onorato JM, Henion JD, Lefebvre PM, Kiplinger JP. Selected reaction monitoring LC-MS determination of idoxifene and its pyrrolidinone metabolite in human plasma using robotic high-throughput, sequential sample injection. Anal Chem. 2001 Jan 1;73(1):119-25. PubMed PMID: 11195494.

16: Yue TL, Vickery-Clark L, Louden CS, Gu JL, Ma XL, Narayanan PK, Li X, Chen J, Storer B, Willette R, Gossett KA, Ohlstein EH. Selective estrogen receptor modulator idoxifene inhibits smooth muscle cell proliferation, enhances reendothelialization, and inhibits neointimal formation in vivo after vascular injury. Circulation. 2000 Nov 7;102(19 Suppl 3):III281-8. PubMed PMID: 11082402.

17: Nuttall ME, Fisher PW, Suva LJ, Gowen M. The selective oestrogen receptor modulators idoxifene and raloxifene have fundamentally different cell-specific oestrogen-response element (ERE)-dependent/independent mechanisms in vitro. Eur J Cancer. 2000 Sep;36 Suppl 4:S63-4. PubMed PMID: 11056323.

18: Ma XL, Gao F, Yao CL, Chen J, Lopez BL, Christopher TA, Disa J, Gu JL, Ohlstein EH, Yue TL. Nitric oxide stimulatory and endothelial protective effects of idoxifene, a selective estrogen receptor modulator, in the splanchnic artery of the ovariectomized rat. J Pharmacol Exp Ther. 2000 Nov;295(2):786-92. PubMed PMID: 11046119.

19: Dowsett M, Dixon JM, Horgan K, Salter J, Hills M, Harvey E. Antiproliferative effects of idoxifene in a placebo-controlled trial in primary human breast cancer. Clin Cancer Res. 2000 Jun;6(6):2260-7. PubMed PMID: 10873076.

20: Badger AM, Blake SM, Dodds RA, Griswold DE, Swift BA, Rieman DJ, Stroup GB, Hoffman SJ, Gowen M. Idoxifene, a novel selective estrogen receptor modulator, is effective in a rat model of adjuvant-induced arthritis. J Pharmacol Exp Ther. 1999 Dec;291(3):1380-6. PubMed PMID: 10565864.

21: Johnston SR, Boeddinghaus IM, Riddler S, Haynes BP, Hardcastle IR, Rowlands M, Grimshaw R, Jarman M, Dowsett M. Idoxifene antagonizes estradiol-dependent MCF-7 breast cancer xenograft growth through sustained induction of apoptosis. Cancer Res. 1999 Aug 1;59(15):3646-51. PubMed PMID: 10446976.

22: Fleischer AC, Wheeler JE, Yeh IT, Kravitz B, Jensen C, MacDonald B. Sonographic assessment of the endometrium in osteopenic postmenopausal women treated with idoxifene. J Ultrasound Med. 1999 Jul;18(7):503-12. PubMed PMID: 10400054.

23: Osborne MR, Hewer A, Davis W, Strain AJ, Keogh A, Hardcastle IR, Phillips DH. Idoxifene derivatives are less reactive to DNA than tamoxifen derivatives, both chemically and in human and rat liver cells. Carcinogenesis. 1999 Feb;20(2):293-7. PubMed PMID: 10069467.

24: Nuttall ME, Bradbeer JN, Stroup GB, Nadeau DP, Hoffman SJ, Zhao H, Rehm S, Gowen M. Idoxifene: a novel selective estrogen receptor modulator prevents bone loss and lowers cholesterol levels in ovariectomized rats and decreases uterine weight in intact rats. Endocrinology. 1998 Dec;139(12):5224-34. PubMed PMID: 9832463.

25: Treinen KA, Rehm S, Wier PJ. An evaluation of the novel selective estrogen receptor modulator, idoxifene, for effects on reproduction in rats and rabbits. Toxicol Sci. 1998 Feb;41(2):199-207. PubMed PMID: 9520356.

26: Jin L, Legros N, Leclercq G, Hardcastle IR, Jarman M. Length increase of the side chain of idoxifene does not improve its antagonistic potency in breast-cancer cell lines. Cancer Chemother Pharmacol. 1998;41(4):339-42. PubMed PMID: 9488604.

27: Pace P, Jarman M, Phillips D, Hewer A, Bliss J, Coombes RC. Idoxifene is equipotent to tamoxifen in inhibiting mammary carcinogenesis but forms lower levels of hepatic DNA adducts. Br J Cancer. 1997;76(6):700-4. PubMed PMID: 9310233; PubMed Central PMCID: PMC2228034.

28: Johnston SR, Riddler S, Haynes BP, A'Hern R, Smith IE, Jarman M, Dowsett M. The novel anti-oestrogen idoxifene inhibits the growth of human MCF-7 breast cancer xenografts and reduces the frequency of acquired anti-oestrogen resistance. Br J Cancer. 1997;75(6):804-9. PubMed PMID: 9062399; PubMed Central PMCID: PMC2063408.

29: Sargent LM, Dragan YP, Sattler C, Bahnub N, Sattler G, Martin P, Cisneros A, Mann J, Thorgeirsson S, Jordan VC, Pitot HC. Induction of hepatic aneuploidy in vivo by tamoxifen, toremifene and idoxifene in female Sprague-Dawley rats. Carcinogenesis. 1996 May;17(5):1051-6. Erratum in: Carcinogenesis 1996 Jun;17(6):1393. PubMed PMID: 8640912.

30: Hardcastle IR, Rowlands MG, Grimshaw RM, Houghton J, Jarman M. Homologs of idoxifene: variation of estrogen receptor binding and calmodulin antagonism with chain length. J Med Chem. 1996 Feb 16;39(4):999-1004. PubMed PMID: 8632423.

31: Young H, Carnochan P, Trivedi M, Potter GA, Eccles SA, Haynes BP, Jarman M, Ott RJ. Pharmacokinetics and biodistribution of radiolabelled idoxifene: prospects for the use of PET in the evaluation of a novel antioestrogen for cancer therapy. Nucl Med Biol. 1995 May;22(4):405-11. PubMed PMID: 7550016.

32: Coombes RC, Haynes BP, Dowsett M, Quigley M, English J, Judson IR, Griggs LJ, Potter GA, McCague R, Jarman M. Idoxifene: report of a phase I study in patients with metastatic breast cancer. Cancer Res. 1995 Mar 1;55(5):1070-4. PubMed PMID: 7866990.

33: Sharp SY, Rowlands MG, Jarman M, Kelland LR. Effects of a new antioestrogen, idoxifene, on cisplatin- and doxorubicin-sensitive and -resistant human ovarian carcinoma cell lines. Br J Cancer. 1994 Sep;70(3):409-14. PubMed PMID: 8080723; PubMed Central PMCID: PMC2033360.