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MedKoo Cat#: 200120 | Name: Afimoxifene
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Description:

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

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

Afimoxifene
Afimoxifene
CAS#68392-35-8

Theoretical Analysis

MedKoo Cat#: 200120

Name: Afimoxifene

CAS#: 68392-35-8

Chemical Formula: C26H29NO2

Exact Mass: 387.2198

Molecular Weight: 387.51

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

Price and Availability

Size Price Availability Quantity
25mg USD 350.00 2 weeks
50mg USD 600.00 2 Weeks
100mg USD 950.00 2 Weeks
200mg USD 1,450.00 2 Weeks
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Related CAS #
68392-35-8 174592-47-3 (E-isomer)
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/.      
Product Data
Product Data
Certificate of Analysis
View CoA: current batch, Lot#C22M09C26
Safety Data Sheet (SDS)
View Safety Data Sheet (SDS)
Instruction
View handling instruction
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 mg/mL 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
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.
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