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Toremifene Citrate (NSC-613680; NK-622; FC-1157a; NSC613680; NSC613680; FC1157a; Fareston), the citrate salt of toremifene, is an orally bioavailable SERM (selective estrogen receptor modulator) approved for use in the treatment of advanced breast cancer. Toremifene citrate acts by antagonizing the actions of estrogen in the body. Toremifene (7.5 mM) causes approximately 60% of the cells to exhibit morphologic characteristics typical of cells undergoing programmed death, or apoptosis in human breast cancer cells. Toremifene (5-10 mM) results in elevated levels of TRPM-2 and TGF beta 1 mRNAs in in vitro or in vivo grown tumor cells.
Physicochemical Properties
| Molecular Formula | C32H36CLNO8 | |
| Molecular Weight | 598.08 | |
| Exact Mass | 597.212 | |
| CAS # | 89778-27-8 | |
| Related CAS # | Toremifene;89778-26-7;Toremifene-d6 citrate;1246833-71-5;Toremifene-d6 hydrochloride | |
| PubChem CID | 3005572 | |
| Appearance | White to off-white solid powder | |
| Density | 1.045g/cm3 | |
| Boiling Point | 535.1ºC at 760 mmHg | |
| Melting Point | 158-164ºC | |
| Flash Point | 277.4ºC | |
| Index of Refraction | 1.416-1.418 | |
| LogP | 4.966 | |
| Hydrogen Bond Donor Count | 4 | |
| Hydrogen Bond Acceptor Count | 9 | |
| Rotatable Bond Count | 14 | |
| Heavy Atom Count | 42 | |
| Complexity | 710 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | CN(C)CCOC1=CC=C(C=C1)/C(=C(/CCCl)\C2=CC=CC=C2)/C3=CC=CC=C3.C(C(=O)O)C(CC(=O)O)(C(=O)O)O |
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| InChi Key | IWEQQRMGNVVKQW-OQKDUQJOSA-N | |
| InChi Code | InChI=1S/C26H28ClNO.C6H8O7/c1-28(2)19-20-29-24-15-13-23(14-16-24)26(22-11-7-4-8-12-22)25(17-18-27)21-9-5-3-6-10-21;7-3(8)1-6(13,5(11)12)2-4(9)10/h3-16H,17-20H2,1-2H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/b26-25-; | |
| Chemical Name | (Z)-2-(4-(4-chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)-N,N-dimethylethan-1-amine 2-hydroxypropane-1,2,3-tricarboxylate | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Toremifene is a second-generation selective estrogen-receptor modulator (SERM) in development for the prevention of osteoporosis and other side effects emerging from ADT with prostate cancer[1]. The proliferation of Ac-1 cells was reduced by tamoxifen, toremifene and atamestane in vitro with IC50values of 1.8±1.3μM, 1±0.3μM and 60.4±17.2μM, respectively. The combination of toremifene + atamestane was found to be better than toremifene or atamestane alone in vitro[3]. | ||
| ln Vivo | After that, the impact of this combination was investigated in vivo utilizing Ac-1 xenografts developed in female SCID mice with ovariectomies. Toremifene (1000μg/day), atamestane (1000μg/day), tamoxifen (100μg/day), or a combination of toremifene and atamestane were injected into the mice. According to the findings of this study, toremifene plus atamestane was just as effective as either drug alone, but it might not have any further advantages over either drug alone[3]. | ||
| Animal Protocol |
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| References |
[1]. Matthew R Smith, Selective Estrogen Receptor Modulators to Prevent Treatment-Related Osteoporosis.Rev Urol. 2005; 7(Suppl 3): S30-S35. [2]. Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors. J Med Chem. 2020 Sep 4. [3]. Gauri J Sabnis, Luciana Macedo, Olga Goloubeva, Toremifene - Atamestane; Alone or In Combination: Predictions from the Preclinical Intratumoral Aromatase Model. J Steroid Biochem Mol Biol. 2008 January; 108(1-2): 1-7. [4]. Taneja SS, Morton R, Barnette G, Prostate cancer diagnosis among men with isolated high-grade intraepithelial neoplasia enrolled onto a 3-year prospective phase III clinical trial of oral toremifene. J Clin Oncol. 2013 Feb 10;31(5):523-9. |
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| Additional Infomation |
Toremifene citrate is a stilbenoid. It has a role as an anticoronaviral agent. Toremifene Citrate is the citrate salt of a nonsteroidal triphenylethylene antiestrogen. Chemically related to tamoxifen, toremifene is a selective estrogen receptor modulator (SERM). This agent binds competitively to estrogen receptors, thereby interfering with estrogen activity. Toremifene also has intrinsic estrogenic properties, which is manifested depending on the tissue or species. (NCI04) A first generation selective estrogen receptor modulator (SERM). Like TAMOXIFEN, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue. See also: Toremifene (has active moiety). Drug Indication First line hormone treatment of hormone-dependent metastatic breast cancer in postmenopausal patients. Fareston is not recommended for patients with estrogen receptor negative tumours. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.18 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6720 mL | 8.3601 mL | 16.7202 mL | |
| 5 mM | 0.3344 mL | 1.6720 mL | 3.3440 mL | |
| 10 mM | 0.1672 mL | 0.8360 mL | 1.6720 mL |