68392-35-8 Usage
Description
Afimoxifene, also known as (E/Z)-4-Hydroxy Tamoxifen, is a first-generation selective estrogen receptor modulator (SERM). It is an off-white solid with the brand name TamoGel, marketed by Ascend Therapeutics. As a SERM, Afimoxifene functions as an antagonist in breast cancer cells, while exhibiting estrogen-like activities in the uterus and bone.
Uses
Used in Pharmaceutical Industry:
Afimoxifene is used as a selective estrogen receptor modulator for the treatment of breast cancer. It acts as an antagonist in breast cancer cells, helping to prevent the growth and spread of cancerous cells.
Used in Hormone Therapy:
Afimoxifene is used as a hormone therapy agent for the management of estrogen-dependent conditions. Its estrogen-like activities in the uterus and bone can help maintain bone health and reduce the risk of osteoporosis.
Used in Research:
Afimoxifene is used as a research tool for studying the mechanisms of estrogen receptor modulation and the development of new therapeutic agents for various diseases, including breast cancer and other hormone-dependent conditions.
Biological Activity
4-hydroxytamoxifen is an estrogen receptor modulator.estrogen receptor can be selectively stimulated or inhibited, providing promising therapeutic opportunities for auto-immune diseases, prostate and breast cancer, as well as depression.
Biochem/physiol Actions
Metabolite of the chemotherapeutic drug tamoxifen, exhibiting more potent estrogen agonist/antagonist activity than the parent drug. Also active as intra-membranous inhibitor of lipid peroxidation.
in vitro
previous study was conducted to evaluate the effects of tamoxifen and its active metabolite 4-hydroxytamoxifen on isolated rat cardiac myocyte mechanical function and calcium handling. results showed that myocytes treated with 4-hydroxytamoxifen had similarly to tamoxifen-treated cells to both calcium handling and contractility [1].
in vivo
previous animal study compared the extent of dna adduct formation in sd rats treated with seven tamoxifen or 4-hydroxytamoxifen. results showed that the liver weights and microsomal rates were not changed by tamoxifen or 4-hydroxytamoxifen treatment. moreover, the uterine weights were significantly decreased and uterine peroxidase activity was marginally decreased in tamoxifen or 4-hydroxytamoxifen treated rats. in addition, hepatic dna adduct levels in rats treated with 4-hydroxytamoxifen did not differ from control rats. similaryly, the adduct levels in uterus dna from rats treated with tamoxifen or 4-hydroxytamoxifen were not different from those in control rats [2].
IC 50
27 and 18 μm for mcf-7 and mda-mb-231 cell proliferation
references
[1] asp ml,martindale jj,metzger jm. direct, differential effects of tamoxifen, 4-hydroxytamoxifen, and raloxifene on cardiac myocyte contractility and calcium handling. plos one.2013 oct 24;8(10):e78768. [2] beland fa,mcdaniel lp,marques mm. comparison of the dna adducts formed by tamoxifen and 4-hydroxytamoxifen in vivo. carcinogenesis.1999 mar;20(3):471-7.[3] lee o et al. a randomized phase ii presurgical trial of transdermal 4-hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in situ of the breast. clin cancer res.2014 jul 15;20(14):3672-82.
Check Digit Verification of cas no
The CAS Registry Mumber 68392-35-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,8,3,9 and 2 respectively; the second part has 2 digits, 3 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 68392-35:
(7*6)+(6*8)+(5*3)+(4*9)+(3*2)+(2*3)+(1*5)=158
158 % 10 = 8
So 68392-35-8 is a valid CAS Registry Number.
InChI:InChI=1/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-
68392-35-8Relevant articles and documents
Synthesis of Tamoxifen-Artemisinin and Estrogen-Artemisinin Hybrids Highly Potent Against Breast and Prostate Cancer
Fr?hlich, Tony,Mai, Christina,Bogautdinov, Roman P.,Morozkina, Svetlana N.,Shavva, Alexander G.,Friedrich, Oliver,Gilbert, Daniel F.,Tsogoeva, Svetlana B.
, p. 1473 - 1479 (2020/07/06)
In the search for new and effective treatments of breast and prostate cancer, a series of hybrid compounds based on tamoxifen, estrogens, and artemisinin were successfully synthesized and analyzed for their in vitro activities against human prostate (PC-3) and breast cancer (MCF-7) cell lines. Most of the hybrid compounds exhibit a strong anticancer activity against both cancer cell lines – for example, EC50 (PC-3) down to 1.07 μM, and EC50 (MCF-7) down to 2.08 μM – thus showing higher activities than their parent compounds 4-hydroxytamoxifen (afimoxifene, 7; EC50=75.1 (PC-3) and 19.3 μM (MCF-7)), dihydroartemisinin (2; EC50=263.6 (PC-3) and 49.3 μM (MCF-7)), and artesunic acid (3; EC50=195.1 (PC-3) and 32.0 μM (MCF-7)). The most potent compounds were the estrogen-artemisinin hybrids 27 and 28 (EC50=1.18 and 1.07 μM, respectively) against prostate cancer, and hybrid 23 (EC50=2.08 μM) against breast cancer. These findings demonstrate the high potential of hybridization of artemisinin and estrogens to further improve their anticancer activities and to produce synergistic effects between linked pharmacophores.
Control of an Unusual Photo-Claisen Rearrangement in Coumarin Caged Tamoxifen through an Extended Spacer
Wong, Pamela T.,Roberts, Edward W.,Tang, Shengzhuang,Mukherjee, Jhindan,Cannon, Jayme,Nip, Alyssa J.,Corbin, Kaitlin,Krummel, Matthew F.,Choi, Seok Ki
, p. 1001 - 1010 (2017/04/27)
The use of coumarin caged molecules has been well documented in numerous photocaging applications including for the spatiotemporal control of Cre-estrogen receptor (Cre-ERT2) recombinase activity. In this article, we report that 4-hydroxytamoxifen (4OHT) caged with coumarin via a conventional ether linkage led to an unexpected photo-Claisen rearrangement which significantly competed with the release of free 4OHT. The basis for this unwanted reaction appears to be related to the coumarin structure and its radical-based mechanism of uncaging, as it did not occur in ortho-nitrobenzyl (ONB) caged 4OHT that was otherwise linked in the same manner. In an effort to perform design optimization, we introduced a self-immolative linker longer than the ether linkage and identified an optimal linker which allowed rapid 4OHT release by both single-photon and two-photon absorption mechanisms. The ability of this construct to actively control Cre-ERT2 mediated gene modifications was investigated in mouse embryonic fibroblasts (MEFs) in which the expression of a green fluorescent protein (GFP) reporter dependent gene recombination was controlled by 4OHT release and measured by confocal fluorescence microscopy and flow cytometry. In summary, we report the implications of this photo-Claisen rearrangement in coumarin caged compounds and demonstrate a rational linker strategy for addressing this unwanted side reaction.
Design of a platinum-acridine-endoxifen conjugate targeted at hormone-dependent breast cancer
Ding, Song,Qiao, Xin,Kucera, Gregory L.,Bierbach, Ulrich
supporting information, p. 2415 - 2417 (2013/04/23)
The synthesis of a novel pharmacophore comprising a DNA-targeted platinum-acridine hybrid agent and estrogen receptor-targeted 4-hydroxy-N-desmethyltamoxifen (endoxifen) using carbamate coupling chemistry and its evaluation in breast cancer cell lines are
