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
Appearance: Solid powder
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 in water
Shelf Life: >2 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
|Biological target:||(E/Z)-4-Hydroxytamoxifen is an estrogen receptor modulator.|
|In vitro activity:||Relative to untreated cells, OHT (Afimoxifene)- treated cells demonstrated a dramatic increase in steady state levels of AVs (Fig.1C). LC3 II can accumulate in response to increased autophagy induction and/or decreased AV degradation. Therefore, autophagic flux was measured in control and OHT-treated cells using BafB1, which inhibits vacuolar ATPase, a molecule active in the late stage of autophagy. OHT- treated cells displayed increased autophagic flux, indicating that the increase in steady state AV levels was due, at least in part, to increased autophagy induction by OHT (Fig.1D). To assess the functional significance of this phenomenon, this study next inhibited the initiation of autophagy by transfecting cells with siRNA targeting Atg7, a critical regulator of AV formation (Fig.1E). Atg7 knockdown partially protected MPNST cells from OHT-induced death (Fig.1F). OHT triggers autophagic death in MPNST cells. Reference: Cancer Res. 2013 Jul 15; 73(14): 4395–4405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715566/|
|In vivo activity:||Fig. 2A illustrates typical examples of a family of total K+ currents (Ipeak) obtained in the same voltage-clamped mouse ventricular myocyte before and after 30 min exposure to 10 µM of 4OH-tamoxifen. Fig. 2B summarizes the corresponding current–voltage (I–V) relationships of Ipeak. At this concentration, 4OH-tamoxifen significantly decreased the density of both the inward and outward portions of Ipeak. Data presented in Fig. 2B also shows that 10 µM of 4OH-tamoxifen significantly decreased the density of the outward portion of the total K+ current for voltages ranging between − 30 and + 50 mV (at + 30 mV, control: 61.3 ± 5.1 pApF− 1; 4OH-tamoxifen: 38.2 ± 4.1 pApF− 1, n = 12, P < 0.01). The density of Ipeak measured at + 30 mV was reduced when the cells were perfused with 0.5 µM of 4OH-tamoxifen from 63.7 ± 4.4 pApF− 1 to 49.4 ± 5.4 pApF− 1 (n = 9; P < 0.05). Similarly, 1 µM 4OH-tamoxifen reduced Ipeak from 62.9 ± 7.0 pApF− 1 to 45.8 ± 5.5 pApF− 1 (n = 10; P < 0.01). Data presented in this figure were obtained from ventricular myocytes isolated from 7 different female mice. Reference: Eur J Pharmacol. 2010 Mar 10;629(1-3):96-103. https://pubmed.ncbi.nlm.nih.gov/20006599/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
|Ethanol:PBS (pH 7.2) (1:2)||0.3||0.77|
The following data is based on the product molecular weight 387.51 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.
|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. Kohli L, Kaza N, Coric T, Byer SJ, Brossier NM, Klocke BJ, Bjornsti MA, Carroll SL, Roth KA. 4-Hydroxytamoxifen induces autophagic death through K-Ras degradation. Cancer Res. 2013 Jul 15;73(14):4395-405. doi: 10.1158/0008-5472.CAN-12-3765. Epub 2013 May 30. PMID: 23722551; PMCID: PMC3715566. 2. Heinen A, Gödecke S, Flögel U, Miklos D, Bottermann K, Spychala A, Gödecke A. 4-hydroxytamoxifen does not deteriorate cardiac function in cardiomyocyte-specific MerCreMer transgenic mice. Basic Res Cardiol. 2021 Feb 5;116(1):8. doi: 10.1007/s00395-020-00841-9. PMID: 33544211; PMCID: PMC7864833. 3. El Gebeily G, Fiset C. 4-Hydroxytamoxifen inhibits K(+) currents in mouse ventricular myocytes. Eur J Pharmacol. 2010 Mar 10;629(1-3):96-103. doi: 10.1016/j.ejphar.2009.12.006. Epub 2009 Dec 16. PMID: 20006599.|
|In vitro protocol:||1. Kohli L, Kaza N, Coric T, Byer SJ, Brossier NM, Klocke BJ, Bjornsti MA, Carroll SL, Roth KA. 4-Hydroxytamoxifen induces autophagic death through K-Ras degradation. Cancer Res. 2013 Jul 15;73(14):4395-405. doi: 10.1158/0008-5472.CAN-12-3765. Epub 2013 May 30. PMID: 23722551; PMCID: PMC3715566.|
|In vivo protocol:||1. Heinen A, Gödecke S, Flögel U, Miklos D, Bottermann K, Spychala A, Gödecke A. 4-hydroxytamoxifen does not deteriorate cardiac function in cardiomyocyte-specific MerCreMer transgenic mice. Basic Res Cardiol. 2021 Feb 5;116(1):8. doi: 10.1007/s00395-020-00841-9. PMID: 33544211; PMCID: PMC7864833. 2. El Gebeily G, Fiset C. 4-Hydroxytamoxifen inhibits K(+) currents in mouse ventricular myocytes. Eur J Pharmacol. 2010 Mar 10;629(1-3):96-103. doi: 10.1016/j.ejphar.2009.12.006. Epub 2009 Dec 16. PMID: 20006599.|
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.
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/.