Afimoxifene
featured

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

Hodoodo CAT#: H200120

CAS#: 68392-35-8

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).


Chemical Structure

img
Afimoxifene
CAS# 68392-35-8

Theoretical Analysis

Hodoodo Cat#: H200120
Name: Afimoxifene
CAS#: 68392-35-8
Chemical Formula: C26H29NO2
Exact Mass: 387.22
Molecular Weight: 387.510
Elemental Analysis: C, 80.59; H, 7.54; N, 3.61; O, 8.26

Price and Availability

Size Price Availability Quantity
10mg USD 250 2 Weeks
25mg USD 450 Ready to ship
50mg USD 750 2 Weeks
Bulk inquiry

Synonym: 4hydroxytamoxifene; 4Hydroxytamoxifen ; Hydroxytamoxifen; Afimoxifene; Tamogel; 4Hydroxytamoxifen ; paraHydroxytamoxifen ; 4Monohydroxytamoxifen ; trans4Hydroxytamoxifen; Tamoxifen metabolite B; 4hydroxytamoxifen.

IUPAC/Chemical Name: 4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenyl-1-buten-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=C1)/C(C2=CC=C(C=C2)OCCN(C)C)=C(CC)\C3=CC=CC=C3

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

More Info: 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/.      

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 54.1 139.64
DMF 20.0 51.61
Ethanol 20.0 51.61
Ethanol:PBS (pH 7.2) (1:2) 0.3 0.77

Preparing Stock Solutions

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.

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. 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.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Hui Y, Luo L, Zhang L, Kurogi K, Zhou C, Sakakibara Y, Suiko M, Liu MC. Sulfation of afimoxifene, endoxifen, raloxifene, and fulvestrant by the human cytosolic sulfotransferases (SULTs): A systematic analysis. J Pharmacol Sci. 2015 Jul;128(3):144-9. doi: 10.1016/j.jphs.2015.06.004. Epub 2015 Jun 25. PMID: 26169578.


2: Koo BK, Stange DE, Sato T, Karthaus W, Farin HF, Huch M, van Es JH, Clevers H. Controlled gene expression in primary Lgr5 organoid cultures. Nat Methods. 2011 Dec 4;9(1):81-3. doi: 10.1038/nmeth.1802. PMID: 22138822.


3: Mansel R, Goyal A, Nestour EL, Masini-Etévé V, O'Connell K; Afimoxifene (4-OHT) Breast Pain Research Group. A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women. Breast Cancer Res Treat. 2007 Dec;106(3):389-97. doi: 10.1007/s10549-007-9507-x. Epub 2007 Mar 10. PMID: 17351746.


4: Feil R, Wagner J, Metzger D, Chambon P. Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains. Biochem Biophys Res Commun. 1997 Aug 28;237(3):752-7. doi: 10.1006/bbrc.1997.7124. PMID: 9299439.


5: Link KH, Shi Y, Koh JT. Light activated recombination. J Am Chem Soc. 2005 Sep 28;127(38):13088-9. doi: 10.1021/ja0531226. PMID: 16173704; PMCID: PMC2512263.


6: Chen G, Yin S, Maiti S, Shao X. 4-Hydroxytamoxifen sulfation metabolism. J Biochem Mol Toxicol. 2002;16(6):279-85. doi: 10.1002/jbt.10048. PMID: 12481303.


7: Goetz MP, Loprinzi CL. A hot flash on tamoxifen metabolism. J Natl Cancer Inst. 2003 Dec 3;95(23):1734-5. doi: 10.1093/jnci/djg129. PMID: 14652227.


8: Walker AK, Enrietto PJ. Regulatable chimeric oncogenes. Methods Enzymol. 1995;254:469-80. doi: 10.1016/0076-6879(95)54032-6. PMID: 8531707.


9: Jordan VC, Allen KE, Dix CJ. Pharmacology of tamoxifen in laboratory animals. Cancer Treat Rep. 1980 Jun-Jul;64(6-7):745-59. PMID: 6775807.


10: Sasaki K, Terasaki M. Estrogen agonistic/antagonistic activity of brominated parabens. Environ Sci Pollut Res Int. 2018 Jul;25(21):21257-21266. doi: 10.1007/s11356-018-2600-3. Epub 2018 Jun 26. PMID: 29946845.


11: Gronemeyer H. Transcription activation by estrogen and progesterone receptors. Annu Rev Genet. 1991;25:89-123. doi: 10.1146/annurev.ge.25.120191.000513. PMID: 1667464.


12: Loren G, Espuny I, Llorente A, Donoghue C, Verdaguer X, Gomis RR, Riera A. Design and optimization of oestrogen receptor PROTACs based on 4-hydroxytamoxifen. Eur J Med Chem. 2022 Dec 5;243:114770. doi: 10.1016/j.ejmech.2022.114770. Epub 2022 Sep 14. PMID: 36148710.


13: Xiong W, Zhao JJ, Wang L, Jiang XH, Tao XQ. [Advances in the research of pharmacogenomics of tamoxifen]. Yao Xue Xue Bao. 2016 Sep;51(9):1356-67. Chinese. PMID: 29924509.


14: Cazzulino AS, Martinez R, Tomm NK, Denny CA. Improved specificity of hippocampal memory trace labeling. Hippocampus. 2016 Jun;26(6):752-62. doi: 10.1002/hipo.22556. Epub 2016 Jan 20. PMID: 26662713; PMCID: PMC4867142.


15: Stroemer P, Hope A, Patel S, Pollock K, Sinden J. Development of a human neural stem cell line for use in recovery from disability after stroke. Front Biosci. 2008 Jan 1;13:2290-2. doi: 10.2741/2842. PMID: 17981710.


16: Jordan VC. Metabolites of tamoxifen in animals and man: identification, pharmacology, and significance. Breast Cancer Res Treat. 1982;2(2):123-38. doi: 10.1007/BF01806449. PMID: 6184101.


17: Ransom RC, Foster DS, Salhotra A, Jones RE, Marshall CD, Leavitt T, Murphy MP, Moore AL, Blackshear CP, Brett EA, Wan DC, Longaker MT. Genetic dissection of clonal lineage relationships with hydroxytamoxifen liposomes. Nat Commun. 2018 Jul 30;9(1):2971. doi: 10.1038/s41467-018-05436-6. Erratum in: Nat Commun. 2018 Oct 19;9(1):4411. PMID: 30061668; PMCID: PMC6065311.


18: Ortiz J, Aranda FJ, Teruel JA, Ortiz A. Dissimilar action of tamoxifen and 4-hydroxytamoxifen on phosphatidylcholine model membranes. Biophys Chem. 2021 Nov;278:106681. doi: 10.1016/j.bpc.2021.106681. Epub 2021 Sep 9. PMID: 34530285.


19: Welsh J. Induction of apoptosis in breast cancer cells in response to vitamin D and antiestrogens. Biochem Cell Biol. 1994 Nov-Dec;72(11-12):537-45. doi: 10.1139/o94-072. PMID: 7654327.


20: Collins GA, Lipford JR, Deshaies RJ, Tansey WP. Gal4 turnover and transcription activation. Nature. 2009 Oct 8;461(7265):E7; discussion E8. doi: 10.1038/nature08406. PMID: 19812621; PMCID: PMC3072683.