MCE products for research use only. We do not sell to patients.

Tamoxifen Citrate

MCE China：Tamoxifen Citrate

Brand：MedChemExpress (MCE)

Cat. No.HY-13757

CAS：54965-24-1

Synonyms：ICI 46474; (Z)-Tamoxifen Citrate; trans-Tamoxifen Citrate

Purity：99.93%

Storage：4°C, sealed storage, away from moisture *In solvent : -80°C, 1 year; -20°C, 6 months (sealed storage, away from moisture)

Shipping：Room temperature in continental US; may vary elsewhere.

Description：Tamoxifen Citrate (ICI 46474) is an orally active, selective estrogen receptor modulator (SERM) which blocks estrogen action in breast cells and can activate estrogen activity in other cells, such as bone, liver, and uterine cells.Tamoxifen Citrate is a potent Hsp90 activator and enhances the Hsp90 molecular chaperone ATPase activity. Tamoxifen Citrate also potent inhibits infectious EBOV Zaire and Marburg (MARV) with IC50 of 0.1 μM and 1.8 μM, respectively. Tamoxifen Citrate activates autophagy and induces apoptosis. Tamoxifen Citrate also can induce gene knockout of CreER transgenic mouse.

In Vitro：Tamoxifen Citrate (ICI 46474) shows strong inhibition of MCF-7 cells (EC50=1.41 μM) and to a lesser extent the T47D cells (EC50=2.5 μM) but does not affect the MDA-MB-231 cells[2].

In Vivo：.f12{ font-size: 12px; } .fwb{ font-weight: bold; } .lh22{ line-height: 22px;; } .lh23 { line-height: 23px; } .pl13{ padding-left: 13px;; } .part { margin-top: 18px; } .mold-first-tit { width: 100%; height: 44px; line-height: 44px; background: #F9F7FB; border-bottom: 1px solid #EBE4F6; padding-left: 16px; box-sizing: border-box; margin-bottom: 17px; } .mold-second-tit:before { content:""; width: 6px; height: 6px; display: inline-block; border-radius: 50%; background: rgba(255,102,0,0.4); margin-right: 12px; position: relative; top: -3px; } .lft-border { border-left: 1px dotted #EBE4F6; padding-right: 12px; margin-left: 3px; box-sizing: border-box; padding-bottom: 12px; } /* .part .dec:last-child { border-bottom: 0; } */ .dec { margin: 10px 15px 0; padding-bottom: 10px; border-bottom: 1px dashed #EBE4F6; } .btm-border { border-left: 1px dashed #EBE4F6; } .text-bg { margin-top: 10px; background: #FFFBF1; padding: 14px; border-bottom: 0; position: relative; } .text-note-bg { margin-top: 10px; background: #FFFDF7; padding: 12px; border-bottom: 0; position: relative; } .text-note { width: 51px; height: 20px; line-height: 20px; background: #FFE2AA; text-align: center; border-radius: 0 0 8px 0; position: absolute; top: 0; left: 0; } .text-note-dec { margin-top: 15px;; } 1. Induction of gene knockout[7][8] Background Gene knockout model induced by tamoxifen uses Cre-Loxp mice. The Cre recombinase in these mice is driven by a tissue/cell-specific promoter, and the target gene is flanked by Loxp sites. The Cre recombinase is fused with the ligand-binding domain of the estrogen receptor to construct a Cre-ER fusion protein, and the recombination activity of Cre is induced by tamoxifen. In the absence of tamoxifen, the Cre-ER fusion protein binds to HSP90 and remains in the cytoplasm. After tamoxifen induction, the metabolite of tamoxifen, 4-OHT, binds to the Cre-ER protein, activates the Cre recombinase, and allows it to enter the nucleus. There, it recognizes the Loxp sites and mediates the knockout of the gene between two (in the same orientation) Loxp sites. (To avoid interference from endogenous estrogens, the ligand-binding domain of the estrogen receptor is modified, transforming Cre-ER into MerCreMer, Cre-ERT, or Cre-ERT2). Specific Mmodeling Methods Mice: Cx3cr1CreERT/+: Pdgfbfl/fl (Conditional knockout of Pdgfb in microglia) Administration: i.p. • 5 consecutive days Note (1) Dissolution: Tamoxifen is poorly soluble in water and is generally dissolved in corn oil. It can be heated at 37°C or sonicated to assist dissolution, ensuring complete dissolution. Tamoxifen should be prepared in the dark and is recommended to be used freshly prepared. Corn oil is relatively viscous. When aspirating the solution, the needle can be left unplugged. After aspirating the solution, attach the needle and expel the air bubbles. (2) Administration methods: Common methods include intraperitoneal injection, and it can also be administered by oral gavage or subcutaneous injection. When performing multiple intraperitoneal injections, the injection sites should be alternated. (3) Dosage: The dosage is 50-120 mg/kg, with 3-5 intraperitoneal injections, usually for 5 consecutive days. The dosage for pregnant mice and aged mice (over 6 months old) should be appropriately reduced. Tamoxifen can affect fetal development and parturition. For pregnant mice, the induction time should preferably be selected in the late pregnancy stage, and progesterone should be injected simultaneously to reduce the probability of miscarriage. (4) Mice: Mice at 4-6 weeks old may be more sensitive (it is more effective in young mice than in old mice). (5) Potential toxicity: Prolonged high-level Cre activity can cause potential toxicity. In addition, if an important functional gene is knocked out, it may also lead to the death of mice. Therefore, close observation should be carried out within one or two weeks after induction. If the mice show abnormalities, the causes need to be analyzed in a timely manner and the experimental plan should be adjusted. (6) Control: Control group mice should be injected with an equal amount of the corn oil solution of tamoxifen (using tamoxifen in a genetic background without Cre recombinase) to rule out the influence of tamoxifen itself. (7) Detection window: The time window between tamoxifen administration and the start of the experiment should be large enough, at least 7 days, to ensure that the Cre recombinase enters the nucleus and functions. (8) Separate caging: Animals treated with tamoxifen should be caged separately from untreated animals to avoid cross - contamination caused by behaviors such as animals licking the oily tamoxifen suspension, grooming their fur, or coprophagy. Modeling Indicators Verify the reduced expression/knockout of the target gene at the RNA or protein level through molecular biology and genetic methods (such as Western blot, PCR, and sequencing, etc.). Correlated Product(s): 4-Hydroxytamoxifen (HY-16950) Opposite Product(s): / 2. Induction of liver injury[9] Background Tamoxifen reduces the hexose monophosphate shunt, thereby increasing the incidence of oxidative stress in rat hepatocytes, leading to liver injury. Specific Mmodeling Methods Albino rat &bull ; female &bull ; period: 7 days Administration: 45 mg/kg •ip • once daily for 7 days Note (1) The rats were kept in a standard laboratory environment, which was a 12-hour light/12-hour dark cycle with the temperature maintained at 25 ± 2°C. They had free access to food and water. (2) At the end of the experiment, the animals were euthanized by cervical dislocation under mild ether anesthesia. The blood samples were collected in heparinized centrifuge tubes and centrifuged to obtain serum. The abdomen was opened, and the liver was immediately dissected and removed. It was washed with ice-cold isotonic saline and blotted between two filter papers. The liver was wrapped in aluminum foil and stored at -80°C. A 10% (w/v) liver homogenate was prepared in ice-cold 0.1 M potassium phosphate buffer (pH 7.5) using an ultrasonicator. Modeling Indicators Molecular Changes: The activities of antioxidant enzymes, including glutathione S-transferase, glutathione peroxidase, and catalase, were significantly ↓, while the content of reduced glutathione also showed a ↓ trend. Concurrently, the levels of thiobarbituric acid reactive substances (TBARS) and liver transaminases, including serum glutamic-pyruvic transaminase (sGPT) and serum glutamic-oxaloacetic transaminase (sGOT), were significantly ↑. Correlated Product(s): / Opposite Product(s): /

Animal Administration：Mice[3]Seven-week old TmcsMed1-/- mice and the wild-type littermates are then administered Tamoxifen intraperitoneally at a daily dose of 65 mg/kg body weight for 5 days and then killed at selected intervals after initiation of Tamoxifen treatment. For each experiment 3 to 5 mice for control and csMed1-/- are used. To obtain survival curve 41 csMed1-/- and 41 csMed1fl/fl mice are used. Thirteen TmcsMed-/- mice and the same number of littermates are used for the survival curve experiments using Tamoxifen inducible model.

IC50 & Target：Estrogen receptor HSP90

Hot selling product：Ammonium glycyrrhizinate  | Larotrectinib sulfate  | NH2-UAMC1110 (TFA)  | Cysteamine (hydrochloride)  | APF  | Psicofuranine  | Sulfadiazine  | N-tert-Butyl-α-phenylnitrone  | Periplogenin  | EAI059

Trending products：Recombinant Proteins  |  Bioactive Screening Libraries  |  Natural Products  |  Fluorescent Dye  |  PROTAC  |  Isotope-Labeled Compounds  |  Oligonucleotides

References：

[1]. Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med. 1998 Nov 26;339(22):1609-18.  [Content Brief]

[2]. Hawariah A, et al. In vitro response of human breast cancer cell lines to the growth-inhibitory effects of styrylpyrone derivative (SPD) and assessment of its antiestrogenicity. Anticancer Res. 1998 Nov-Dec;18(6A):4383-6.  [Content Brief]

[3]. Jia Y, et al. Cardiomyocyte-Specific Ablation of Med1 Subunit of the Mediator Complex Causes Lethal DilatedCardiomyopathy in Mice. PLoS One. 2016 Aug 22;11(8):e0160755.  [Content Brief]

[4]. Zhao R, et al. Tamoxifen enhances the Hsp90 molecular chaperone ATPase activity. PLoS One. 2010 Apr 1;5(4):e9934.  [Content Brief]

[5]. Laura Cooper, et al. Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors. J Med Chem. 2020 Sep 4.  [Content Brief]

[6]. Feil S, et, al. Inducible Cre mice. Methods Mol Biol. 2009;530:343-63.  [Content Brief]

[7]. Bi Q, et al. Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension. Immunity. 2022 Aug 9;55(8):1466-1482.e9.  [Content Brief]

[8]. Chen MY, et al. A review of tamoxifen administration regimen optimization for Cre/loxp system in mouse bone study. Biomed Pharmacother. 2023 Sep;165:115045.  [Content Brief]

[9]. Sohal DS, et al. Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein. Circ Res. 2001 Jul 6;89(1):20-5.  [Content Brief]