FLTX1
目录号 : GC62484
FLTX1 是一种荧光他莫昔芬 (Tamoxifen) 衍生物，可以在透化和非透化条件下特异性标记细胞内 Tamoxifen 结合位点 (雌激素受体)。FLTX1 在乳腺癌细胞中表现出 Tamoxifen 有效的抗雌激素特性。FLTX1 缺乏对子宫的雌激素激动作用。
Cas No.:1481401-71-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
FLTX1 is a fluorescent Tamoxifen derivative that can specifically label intracellular Tamoxifen-binding sites (estrogen receptors) under permeabilized and non-permeabilized conditions. FLTX1 exhibits the potent antiestrogenic properties of Tamoxifen in breast cancer cells. FLTX1 is devoid of the estrogenic agonistic effect on the uterus[1][2].
FLTX1 (0.01-10 μM; 6 d) reduces MCF7 cell proliferation in a dose-dependent manner. FLTX1 (pretreated 24 h) counteracts the increase in cell growth induced by E2 down to the vehicle level[1].FLTX1 (50 μM; 2 h) exhibits a dose-dependent competition with Tamoxifen (Tx) in MCF7 cells[1].FLTX1 (0.1 nM-100 μM; 18 h) competitively displaces the [3H] E2 binding to rat uterine estrogen receptors (ER) rat uterus cytosol, with an IC50 of 87.5 nM[1].FLTX1 (0.1 nM-10 μM; pretreated 8 h) reduces the estradiol-induced luciferase expression activity in a dose-dependent manner. FLTX1 (15-16 h) is devoid of the potent estrogenic agonist activity in both transiently transfected MCF7 cells and stably transfected T47D-KBluc cells[1].
FLTX1 (0.01-1 mg/kg/d; s.c. for 3 d) is lacked of the estrogenic uterotrophic (and also cervical and vaginal), hyperplasic and hypertrophic effects, and failed to alter basal proliferating cell nuclear antigen immunoreactivity in mice and rats[1].
[1]. Marrero-Alonso J, et, al. Unique SERM-like properties of the novel fluorescent tamoxifen derivative FLTX1. Eur J Pharm Biopharm. 2013 Nov;85(3 Pt B):898-910.
[2]. Morales A, et, al. Colocalization of Estrogen Receptors with the Fluorescent Tamoxifen Derivative, FLTX1, Analyzed by Confocal Microscopy. Methods Mol Biol. 2016;1366:163-173.
| Cas No. | 1481401-71-1 | SDF | |
| 分子式 | C31H28N4O4 | 分子量 | 520.58 |
| 溶解度 | DMSO : 25 mg/mL (48.02 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9209 mL | 9.6047 mL | 19.2093 mL |
| 5 mM | 0.3842 mL | 1.9209 mL | 3.8419 mL |
| 10 mM | 0.1921 mL | 0.9605 mL | 1.9209 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Unique SERM-like properties of the novel fluorescent tamoxifen derivative FLTX1
Eur J Pharm Biopharm 2013 Nov;85(3 Pt B):898-910.PMID:23727370DOI:10.1016/j.ejpb.2013.04.024.
Tamoxifen is a selective estrogen receptor modulator extensively used on estrogen receptor-positive breast cancer treatment. However, clinical evidences demonstrate the increased incidence of undesirable side effects during chronic therapies, the most life threatening being uterine cancers. Some of these effects are related to tissue-dependent estrogenic actions of tamoxifen, but the exact mechanisms remain poorly understood. We have designed and synthesized a novel fluorescent tamoxifen derivative, FLTX1, and characterized its biological and pharmacological activities. Using confocal microscopy, we demonstrate that FLTX1 colocalizes with estrogen receptor α (ERα). Competition studies showed that FLTX1 binding was totally displaced by unlabeled tamoxifen and partially by estradiol, indicating the existence of non-ER-related triphenylethylene-binding sites. Ligand binding assays showed that FLTX1 exhibits similar affinity for ER than tamoxifen. FLTX1 exhibited antiestrogenic activity comparable to tamoxifen in MCF7 and T47D cells transfected with 3xERE-luciferase reporter. Interestingly, FLTX1 lacked the strong agonistic effect of tamoxifen on ERα-dependent transcriptional activity. Additionally, in vivo assays in mice revealed that unlike tamoxifen, FLTX1 was devoid of estrogenic uterotrophic effects, lacked of hyperplasic and hypertrophic effects, and failed to alter basal proliferating cell nuclear antigen immunoreactivity. In the rat uterine model of estrogenicity/antiestrogenicity, FLTX1 displayed antagonistic activity comparable to tamoxifen at lower doses, and only estrogenic uterotrophy at the highest dose. We conclude that the fluorescent derivative FLTX1 is not only a suitable probe for studies on the molecular pharmacology of tamoxifen, but also a potential therapeutic substitute to tamoxifen, endowed with potent antiestrogenic properties but devoid of uterine estrogenicity.
Colocalization of Estrogen Receptors with the Fluorescent Tamoxifen Derivative, FLTX1, Analyzed by Confocal Microscopy
Methods Mol Biol 2016;1366:163-173.PMID:26585134DOI:10.1007/978-1-4939-3127-9_13.
Tamoxifen is a selective estrogen receptor modulator that competitively binds the ligand-binding domain of estrogen receptors. Binding of tamoxifen displaces its cognate ligand, 17β-estradiol, thereby hampering the activation of estrogen receptors. Cellular labeling of ER is typically carried out using specific antibodies which require permeabilization of cells, incubation with secondary antibodies, and are expensive and time consuming. In this article, we describe the usefulness of FLTX1, a novel fluorescent tamoxifen derivative, which allows the labeling of estrogen receptors in immunocytochemistry and immunohistochemistry studies, both under permeabilized and non-permeabilized conditions. Further, besides labeling canonical estrogen receptors, this novel fluorescent probe is also suitable for the identification of unconventional targets such membrane estrogen receptors as well as other noncanonical targets, some of which are likely responsible for the number of undesired side effects reported during long-term tamoxifen treatments.
FRET mechanism between a fluorescent breast-cancer drug and photodynamic therapy sensitizers
Spectrochim Acta A Mol Biomol Spectrosc 2020 Oct 5;239:118498.PMID:32470814DOI:10.1016/j.saa.2020.118498.
Tamoxifen is one of the most frequently used drugs for the treatment of estrogen receptor positive breast cancer, which is the most prevalent form of hormone dependent breast cancer. A few years ago, we developed a fluorescent derivative of tamoxifen formed by the covalent binding of tamoxifen to a common dye biomarker. The new compound, known as FLTX1, showed the pharmacological activity of the tamoxifen moiety and efficient fluorescence properties, which could be used synergistically to improve the effect of the drug. In this paper, we demonstrate that irradiation at the absorption band of FLTX1 can result in fluorescence resonance energy transfer to photosensitizers such as Rose Bengal and Merocyanine 540, activating the production of reactive oxygen species (ROS). Indeed, the generation of ROS was demonstrated using a colorimetric assay. Since FLTX1 mostly binds estrogen-receptor overexpressing cancer cells, the results obtained are very promising and suggest a new therapeutic strategy combining chemo- and photodynamic therapies.
FLTX2: A Novel Tamoxifen Derivative Endowed with Antiestrogenic, Fluorescent, and Photosensitizer Properties
Int J Mol Sci 2021 May 19;22(10):5339.PMID:34069498DOI:10.3390/ijms22105339.
Tamoxifen is the most widely used selective modulator of estrogen receptors (SERM) and the first strategy as coadjuvant therapy for the treatment of estrogen-receptor (ER) positive breast cancer worldwide. In spite of such success, tamoxifen is not devoid of undesirable effects, the most life-threatening reported so far affecting uterine tissues. Indeed, tamoxifen treatment is discouraged in women under risk of uterine cancers. Recent molecular design efforts have endeavoured the development of tamoxifen derivatives with antiestrogen properties but lacking agonistic uterine tropism. One of this is FLTX2, formed by the covalent binding of tamoxifen as ER binding core, 7-nitrobenzofurazan (NBD) as the florescent dye, and Rose Bengal (RB) as source for reactive oxygen species. Our analyses demonstrate (1) FLTX2 is endowed with similar antiestrogen potency as tamoxifen and its predecessor FLTX1, (2) shows a strong absorption in the blue spectral range, associated to the NBD moiety, which efficiently transfers the excitation energy to RB through intramolecular FRET mechanism, (3) generates superoxide anions in a concentration- and irradiation time-dependent process, and (4) Induces concentration- and time-dependent MCF7 apoptotic cell death. These properties make FLTX2 a very promising candidate to lead a novel generation of SERMs with the endogenous capacity to promote breast tumour cell death in situ by photosensitization.