WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200120
Description: 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).
MedKoo Cat#: 200120
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
Synonym: 4hydroxytamoxifene; 4Hydroxytamoxifen ; Hydroxytamoxifen; Afimoxifene; Tamogel; 4Hydroxytamoxifen ; paraHydroxytamoxifen ; 4Monohydroxytamoxifen ; trans4Hydroxytamoxifen; Tamoxifen metabolite B; 4hydroxytamoxifen.
IUPAC/Chemical Name: (E)-4-(1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenol
InChi Key: TXUZVZSFRXZGTL-OCEACIFDSA-N
InChi Code: InChI=1S/C26H29NO2/c1-4-25(20-8-6-5-7-9-20)26(21-10-14-23(28)15-11-21)22-12-16-24(17-13-22)29-19-18-27(2)3/h5-17,28H,4,18-19H2,1-3H3/b26-25+
SMILES Code: OC1=CC=C(/C(C2=CC=C(OCCN(C)C)C=C2)=C(C3=CC=CC=C3)/CC)C=C1
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/.
1: Hui RC, Francis RE, Guest SK, Costa JR, Gomes AR, Myatt SS, Brosens JJ, Lam EW. Doxorubicin activates FOXO3a to induce the expression of multidrug resistance gene ABCB1 (MDR1) in K562 leukemic cells. Mol Cancer Ther. 2008 Mar;7(3):670-8. PubMed PMID: 18347152.
2: Yu D, Carroll M, Thomas-Tikhonenko A. p53 status dictates responses of B lymphomas to monotherapy with proteasome inhibitors. Blood. 2007 Jun 1;109(11):4936-43. Epub 2007 Feb 6. PubMed PMID: 17284530; PubMed Central PMCID: PMC1885530.
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, CustÃ³dio 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.