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MedKoo product information:

 Afimoxifene

 

Description of afimoxifene: Afimoxifene (4-hydroxytamoxifen) is a selective estrogen receptor modulator which is the active metabolite of tamoxifen. Afimoxifene is a transdermal gel formulation and is being developed by Ascend Therapeutics, Inc. under the trademark TamoGel. Afimoxifene has completed a phase II clinical trial for the treatment of cyclical mastalgia. A study in France on 55 women showed that rubbing afimoxifene on the skin was as good as tamoxifen tablets at slowing breast cancer growth. A US trial will compare 6 weeks use before breast cancer surgery. Skin application can reduce systemic levels by a factor of nine and this is expected to reduce the unpleasant side-effects of tamoxifen. (source: http://en.wikipedia.org/wiki/Afimoxifene).

  

Current developer:    Ascend Therapeutics, Inc.

  

MedKoo Code#:  200120

Name:  Afimoxifene

CAS#:  68392-35-8

  

Synonym:   4-hydroxytamoxifene;  4-Hydroxytamoxifen ; Hydroxytamoxifen; Afimoxifene; Tamogel; 4-Hydroxy-tamoxifen ; para-Hydroxytamoxifen ; 4-Monohydroxytamoxifen ; trans-4-Hydroxytamoxifen; Tamoxifen metabolite B ; 4'-hydroxytamoxifen

   

IUPAC/Chemical name: 

(E)-4-(1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenol

 

Chemical structure Theoretical analysis

 

 

  

Chemical Formula: C26H29NO2

Exact Mass: 387.21983

Molecular Weight: 387.51

Elemental Analysis: C, 80.59; H, 7.54; N, 3.61; O, 8.26

  

  

Availability and price:

 

Afimoxifene is available through custom synthesis.

  

To inquire quotation and lead time or to ask questions, please send email to sales@medkoo.com to describe your needs. A representative will respond your email shortly. We offer big discount for orders of bulk quantities.

 

Quality control data:

Product will be shipped with supporting analytical data.

  

 

Information about this agent

Afimoxifene gel is ASCEND's lead product, which is  an antiestrogen being evaluated for the treatment of cyclic breast pain and other estrogen dependent disorders in premenopausal women. Results of a Phase 2 clinical trial of afimoxifene gel indicate that the treatment was well tolerated and showed a statistically significant reduction in cyclic breast pain. In this trial, headaches were the most common side effect, which were in general mild and similar across treatment groups. ASCEND also believes that afimoxifene gel has the potential to treat a broad range of estrogen-related conditions. A multi-center, Phase 2 trial of afimoxifene gel vs. oral tamoxifen in women with ductal carcinoma in situ (DCIS) of the breast will be conducted by the National Cancer Prevention Group Consortium starting in the second quarter of 2009. This trial is being coordinated by the National Institutes of Health/National Cancer Institute.  see http://www.ascendtherapeutics.com/about/.

 

 

References

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3: Sadler TM, Gavriil M, Annable T, Frost P, Greenberger LM, Zhang Y. Combination therapy for treating breast cancer using antiestrogen, ERA-923, and the mammalian target of rapamycin inhibitor, temsirolimus. Endocr Relat Cancer. 2006 Sep;13(3):863-73. PubMed PMID: 16954435.

4: Murata S, Kominsky SL, Vali M, Zhang Z, Garrett-Mayer E, Korz D, Huso D, Baker SD, Barber J, Jaffee E, Reilly RT, Sukumar S. Ductal access for prevention and therapy of mammary tumors. Cancer Res. 2006 Jan 15;66(2):638-45. PubMed PMID: 16423990.

5: Kisanga ER, Moi LL, Gjerde J, Mellgren G, Lien EA. Induction of hepatic drug-metabolising enzymes and tamoxifen metabolite profile in relation to administration route during low-dose treatment in nude rats. J Steroid Biochem Mol Biol. 2005 Apr;94(5):489-98. Epub 2005 Apr 7. PubMed PMID: 15876414.

6: Maillard S, Ameller T, Gauduchon J, Gougelet A, Gouilleux F, Legrand P, Marsaud V, Fattal E, Sola B, Renoir JM. Innovative drug delivery nanosystems improve the anti-tumor activity in vitro and in vivo of anti-estrogens in human breast cancer and multiple myeloma. J Steroid Biochem Mol Biol. 2005 Feb;94(1-3):111-21. Epub 2005 Jan 27. PubMed PMID: 15862956.

7: Demaria S, Santori FR, Ng B, Liebes L, Formenti SC, Vukmanovic S. Select forms of tumor cell apoptosis induce dendritic cell maturation. J Leukoc Biol. 2005 Mar;77(3):361-8. Epub 2004 Nov 29. PubMed PMID: 15569694.

8: Monteiro JP, Martins JD, Luxo PC, Jurado AS, Madeira VM. Molecular mechanisms of the metabolite 4-hydroxytamoxifen of the anticancer drug tamoxifen: use of a model microorganism. Toxicol In Vitro. 2003 Oct-Dec;17(5-6):629-34. PubMed PMID: 14599455.

9: Cruz Silva MM, Madeira VM, Almeida LM, Custódio JB. Hydroxytamoxifen interaction with human erythrocyte membrane and induction of permeabilization and subsequent hemolysis. Toxicol In Vitro. 2001 Dec;15(6):615-22. PubMed PMID: 11698160.

10: Montano MM, Katzenellenbogen BS. The quinone reductase gene: a unique estrogen receptor-regulated gene that is activated by antiestrogens. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2581-6. PubMed PMID: 9122238; PubMed Central PMCID: PMC20131.

11: Lu W, Poon GK, Carmichael PL, Cole RB. Analysis of tamoxifen and its metabolites by on-line capillary electrophoresis-electrospray ionization mass spectrometry employing nonaqueous media containing surfactants. Anal Chem. 1996 Feb 15;68(4):668-74. PubMed PMID: 8999741.

12: Jarman M, Poon GK, Rowlands MG, Grimshaw RM, Horton MN, Potter GA, McCague R. The deuterium isotope effect for the alpha-hydroxylation of tamoxifen by rat liver microsomes accounts for the reduced genotoxicity of [D5-ethyl]tamoxifen. Carcinogenesis. 1995 Apr;16(4):683-8. PubMed PMID: 7728943.

13: Rao US, Fine RL, Scarborough GA. Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92. PubMed PMID: 7914405.

14: Custódio JB, Dinis TC, Almeida LM, Madeira VM. Tamoxifen and hydroxytamoxifen as intramembraneous inhibitors of lipid peroxidation. Evidence for peroxyl radical scavenging activity. Biochem Pharmacol. 1994 Jun 1;47(11):1989-98. PubMed PMID: 8010983.

15: Wiseman H. The antioxidant action of a pure antioestrogen: ability to inhibit lipid peroxidation compared to tamoxifen and 17 beta-oestradiol and relevance to its anticancer potential. Biochem Pharmacol. 1994 Feb 9;47(3):493-8. PubMed PMID: 8117317.

16: Custódio JB, Almeida LM, Madeira VM. The active metabolite hydroxytamoxifen of the anticancer drug tamoxifen induces structural changes in membranes. Biochim Biophys Acta. 1993 Dec 12;1153(2):308-14. PubMed PMID: 8274502.

17: Wiseman H, Quinn P, Halliwell B. Tamoxifen and related compounds decrease membrane fluidity in liposomes. Mechanism for the antioxidant action of tamoxifen and relevance to its anticancer and cardioprotective actions? FEBS Lett. 1993 Sep 6;330(1):53-6. PubMed PMID: 8370459.

18: Jiang SY, Parker CJ, Jordan VC. A model to describe how a point mutation of the estrogen receptor alters the structure-function relationship of antiestrogens. Breast Cancer Res Treat. 1993;26(2):139-47. PubMed PMID: 8219251.

19: Custódio JB, Almeida LM, Madeira VM. A reliable and rapid procedure to estimate drug partitioning in biomembranes. Biochem Biophys Res Commun. 1991 May 15;176(3):1079-85. PubMed PMID: 2039491.

20: Murphy CS, Parker CJ, McCague R, Jordan VC. Structure-activity relationships of nonisomerizable derivatives of tamoxifen: importance of hydroxyl group and side chain positioning for biological activity. Mol Pharmacol. 1991 Mar;39(3):421-8. PubMed PMID: 2005879.

21: Wiseman H, Smith C, Arnstein HR, Halliwell B, Cannon M. The antioxidant action of ketoconazole and related azoles: comparison with tamoxifen and cholesterol. Chem Biol Interact. 1991;79(2):229-43. PubMed PMID: 1884432.

22: Wiseman H, Cannon M, Arnstein HR, Halliwell B. Mechanism of inhibition of lipid peroxidation by tamoxifen and 4-hydroxytamoxifen introduced into liposomes. Similarity to cholesterol and ergosterol. FEBS Lett. 1990 Nov 12;274(1-2):107-10. PubMed PMID: 2253763.

 

 

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