托瑞米芬是第二代选择性雌激素受体调节剂 (SERM)，正在开发用于阻止骨质疏松症和 ADT 诱导的前列腺癌的其他副作用 [1]。他莫昔芬、托瑞米芬和阿他美坦体外抑制Ac-1细胞的增殖，IC50值分别为1.8±1.3μM、1±0.3μM和60.4±17.2μM。根据体外研究，托瑞米芬和阿他美坦的组合比单独使用任何一种药物更有效[3]。

之后，利用在卵巢切除的雌性 SCID 小鼠中开发的 Ac-1 异种移植物在体内研究了这种组合的影响。将托瑞米芬（1000μg/天）、阿他美坦（1000μg/天）、他莫昔芬（100μg/天）或托瑞米芬和阿他美坦的组合注射到小鼠体内。这项调查的结果表明，托瑞米芬加阿他美坦与单独使用任一药物一样有效，尽管可能并不比单独使用任一药物更有效。使用他莫昔芬没有其他好处[3]。

Absorption, Distribution and Excretion
Well absorbed
Toremifene is extensively metabolized, principally by CYP3A4 to N-demethyltoremifene, which is also antiestrogenic but with weak in vivo antitumor potency.
580 L
5 L/h

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Metabolism / Metabolites
Hepatic. Mainly by CYP3A4 to N-demethyltoremifene, which exhibits antiestrogenic effects but has weak antitumor potency in vivo.
Toremifene has known human metabolites that include N-desmethyltoremifene.

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Biological Half-Life
5 days

Hepatotoxicity
Toremifene has been associated with mild-to-moderate serum ALT or AST elevations in 5% to 19% of patients, but these abnormalities are usually transient and not associated with symptoms or jaundice. Elevations above 5 times the ULN are uncommon (
Likelihood score: D (possible cause of clinically apparent liver injury).

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Protein Binding
Toremifen is primarily bound to albumin (92%), 2% bound to α1-acid glycoprotein, and 6% bound to β1-globulin in the serum.

[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.

Toremifene is a tertiary amine, an organochlorine compound and an aromatic ether. It has a role as an antineoplastic agent, an estrogen antagonist, an estrogen receptor modulator and a bone density conservation agent. It derives from a hydride of a stilbene.
Toremifene is a selective estrogen receptor modulator (SERM) and a nonsteroidal antiestrogen used to treat estrogen receptor positive breast cancer. Like [tamoxifen], toremifene is part of the first-generation triphenylethylene derivative chemical class of SERMs. Toremifene possesses tissue-specific actions: it has estrogenic (agonist) activity on the cardiovascular system and on bone tissue and it has weak estrogenic effects on uterine tissue, however, it also has antiestrogenic (estrogen-antagonist) activity on breast tissue.
Toremifene is an Estrogen Agonist/Antagonist. The mechanism of action of toremifene is as a Selective Estrogen Receptor Modulator.
Toremifene is a nonsteroidal antiestrogen that is used in the treatment of estrogen receptor positive breast cancer. Long term toremifene therapy has been associated with development of fatty liver, steatohepatitis, cirrhosis, and rare instances of clinically apparent acute liver injury.
Toremifene is 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 are manifested according to tissue type 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 Citrate (has salt form).

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Drug Indication
For the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor-positive or receptor-unknown tumors. Toremifene is currently under investigation as a preventative agent for prostate cancer in men with high-grade prostatic intraepithelial neoplasia and no evidence of prostate cancer.
First line hormone treatment of hormone-dependent metastatic breast cancer in postmenopausal patients. Fareston is not recommended for patients with estrogen receptor negative tumours.

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Mechanism of Action
Toremifene is a nonsteroidal triphenylethylene derivative. Toremifene binds to estrogen receptors and may exert estrogenic, antiestrogenic, or both activities, depending upon the duration of treatment, animal species, gender, target organ, or endpoint selected. The antitumor effect of toremifene in breast cancer is believed to be mainly due to its antiestrogenic effects, in other words, its ability to compete with estrogen for binding sites in the cancer, blocking the growth-stimulating effects of estrogen in the tumor. Toremifene may also inhibit tumor growth through other mechanisms, such as induction of apoptosis, regulation of oncogene expression, and growth factors.

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Pharmacodynamics
Toremifene is an antineoplastic hormonal agent primarily used in the treatment of advanced breast cancer. Toremifene is a nonsteroidal agent that has demonstrated potent antiestrogenic properties in animal test systems. The antiestrogenic effects may be related to its ability to compete with estrogen for binding sites in target tissues such as breast. Toremifene inhibits the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes the regression of already established DMBA-induced tumors. In this rat model, Toremifene appears to exert its antitumor effects by binding the estrogen receptors. In cytosols derived from human breast adenocarcinomas, Toremifene competes with estradiol for estrogen receptor protein.

C26H28CLNO

405.97

405.185

89778-26-7

Toremifene citrate;89778-27-8;Toremifene-d6;Toremifene-d6 hydrochloride

3005573

White to light yellow solid powder

1.1±0.1 g/cm3

535.1±50.0 °C at 760 mmHg

108-110°C

277.4±30.1 °C

0.0±1.4 mmHg at 25°C

1.588

7.82

12.47

0

2

9

29

483

0

CN(C)CCOC1=CC=C(C=C1)/C(=C(/CCCl)\C2=CC=CC=C2)/C3=CC=CC=C3

XFCLJVABOIYOMF-QPLCGJKRSA-N

InChI=1S/C26H28ClNO/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/h3-16H,17-20H2,1-2H3/b26-25-

Ethanamine, 2-(4-((1Z)-4-chloro-1,2-diphenyl-1-butenyl)phenoxy)-N,N-dimethyl-

GTx 006 Z-Toremifene Acapodene Farestone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。