Zuclomiphene acts as an estrogen receptor antagonist, binding to cytoplasmic and nuclear estrogen receptors [3]

在鸡输卵管制备物中，珠氯米芬（Zuclomiphene）通过与雌激素竞争结合胞质和核雌激素受体而发挥抗雌激素活性。它能抑制输卵管中雌激素诱导的反应，表现为雌激素依赖性生物活性降低 [3]

在雄性小鼠中，给予珠氯米芬（Zuclomiphene）（100 μg/天，皮下注射）28天，与对照组相比，睾丸重量显著增加。它还会导致附睾重量增加，并影响精子参数，包括精子数量和活力的变化。此外，它可调节生殖组织形态，包括曲细精管结构的改变 [1]

在鸡输卵管胞质和核组分实验中，将珠氯米芬（Zuclomiphene）与这些组分在放射性标记雌激素存在的条件下共同孵育。通过测量放射性标记雌激素的置换来评估珠氯米芬（Zuclomiphene）与雌激素受体的结合，从而量化其对受体的亲和力 [3]

For male mice studies, adult male mice are subcutaneously injected with Zuclomiphene at a dose of 100 μg/day for 28 days. Control groups receive vehicle injections. At the end of the treatment period, mice are euthanized, and reproductive tissues (testes, epididymides) are harvested for weight measurement, histological analysis, and sperm parameter evaluation [1]

Absorption, Distribution and Excretion
Based on early studies with 14 C-labeled clomifene, the drug was shown to be readily absorbed orally in humans.
Based on early studies with 14C-labeled clomiphene citrate, the drug was shown to be readily absorbed orally in humans and excreted principally in the feces. Mean urinary excretion was approximately 8% with fecal excretion of about 42%.
SC DOSE OF (14)C CLOMIPHENE CITRATE...WAS DISTRIBUTED IN TISSUES OF FEMALE GUINEA PIG NEONATES... ESTROGENIC-RESPONSIVE TISSUES SHOWED HIGH AFFINITY FOR (14)C. LEVELS OF (14)C...CONSTANT IN UTERUS...THOSE IN OVARIES & PLASMA DECLINED...IN ADRENALS INCR. /CLOMIPHENE CITRATE/
ABOUT ONE-HALF OF THE INGESTED DOSE IS EXCRETED IN FIVE DAYS; TRACES APPEAR IN THE FECES UP TO SIX WEEKS AFTER ADMIN. /CLOMIPHENE CITRATE/
Clomiphene is well absorbed following oral administration. The drug and its metabolites are eliminated primarily in the feces and to a lesser extent in the urine. The rather long plasma half-life (approximately 5 to 7 days) is due largely to plasma protein binding, enterophepatic circulation, and accumulation in fatty tissues. Active metabolites with long half-lives also may be produced.

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Metabolism / Metabolites
Hepatic
INCUBATION OF THE NONSTEROIDAL ANTIESTROGEN CLOMIPHENE WITH RAT LIVER MICROSOMES RESULTED IN THE FORMATION OF THE 4-HYDROXY-, N-DESETHYL-, & N-OXIDE METABOLITES, IN QUALITATIVE CONTRAST TO RESULTS PREVIOUSLY OBTAINED ANALOGOUSLY WITH RABBIT MICROSOMES IN WHICH ONLY THE FIRST 2 METABOLITES WERE DETECTED. ORAL ADMIN OF CLOMIPHENE RESULTED IN NO DETECTABLE URINARY ELIMINATION OF THE DRUG OR ITS METABOLITES. 4-HYDROXYCLOMIPHENE WAS THE SOLE DETECTABLE ELIMINATION PRODUCT IN FECAL EXTRACTIONS.

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Biological Half-Life
5-7 days

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After a single oral dose of clomiphene citrate (which contains Zuclomiphene as an isomer) in normal volunteers, Zuclomiphene shows a longer elimination half-life compared to the other isomer (enclomiphene). It persists in plasma for an extended period, with detectable levels up to several weeks post-administration [2]

Hepatotoxicity
There is little information on serum aminotransferase levels during clomiphene therapy which is typically given in low doses for a short time only. There have been a few reports of mild serum enzyme elevations in patients taking clomiphene, but no convincing instances of idiosyncratic, clinically apparent liver injury with its use.
Drugs used to treat infertility in women typically act by stimulation of the ovarian follicles which can lead to the ovarian hyperstimulation syndrome (OHSS), which can occasionally be accompanied by serum enzyme elevations and even jaundice. This syndrome typically arises within 4 to 14 days of ovarian stimulation with gonadotropins or clomiphene and is characterized by the onset of abdominal pain and distension with ascites and enlarged ovaries and ovarian cysts. There can be marked fluid shifts with hemoconcentration and rapid onset of severe ascites and pleural effusions. Liver tests are elevated in 25% to 40% of patients with OHSS, typically with mild-to-moderate increases in ALT and AST values, but minimal or no elevations in serum bilirubin and alkaline phosphatase levels. The liver test abnormalities resolve with resolution of the OHSS, usually within 2 to 3 weeks of onset. In severe instances, OHSS can be fatal, but death is usually due to dehydration, shock and septicemia rather than hepatic failure. In typical cases with abnormal liver enzymes, liver histology reveals nonspecific changes of sinusoidal dilatation, mild fat accumulation and focal inflammatory infiltrates with macrophages and lymphocytes. OHSS is less common with clomiphene than with human chorionic gonadotropin (hCG) induction of ovulation.
Likelihood score: C (probable cause of clinically apparent liver injury as a part of the ovarian hyperstimulation syndrome).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Clomiphene appeared in low amounts in milk in one woman. Several studies found that clomiphene suppresses lactation in women who did not want to breastfeed. It appears to act by lowering serum prolactin, especially the post-stimulation surge in serum prolactin. It is likely that clomiphene would interfere with lactation in a nursing mother.
◉ Effects in Breastfed Infants
A woman who was taking clomiphene in a dose of 2.04 mg/kg daily partially breastfed her infant. She did not observe any adverse effects in her infant.
◉ Effects on Lactation and Breastmilk
A double-blind study compared clomiphene in dosages of 50 mg daily for 10 days (n = 110), 100 mg daily for 5 days (n = 26) and placebo (n = 41) in their ability to suppress lactation and relieve pain and engorgement in nonnursing postpartum mothers. Both dosages of clomiphene were superior to placebo as reported by the women, but the 100 mg daily dosage was somewhat superior to the 50 mg daily dosage.
A study compared clomiphene 100 mg daily for 5 days (n = 60) to placebo (n = 30) in suppressing lactation and symptoms of engorgement. Starting clomiphene within 12 hours of delivery was more effective in all measures than starting it 12 hours or more after delivery as judged by a physician observer; both treatments were more effective than mechanical measures alone such as breast binding.
A randomized trial compared clomiphene 50 mg twice daily for 14 days (n = 15) to bromocriptine 2.5 mg twice daily for 14 days (n = 15), diethylstilbestrol 5 mg 3 times daily for 14 days (n = 15), testosterone propionate 75 mg intramuscularly once (n = 15), and placebo 3 times daily by mouth (n = 15) in their ability to reduce serum prolactin and lactation postpartum. After three days of treatment, serum prolactin was reduced to 65% of baseline by clomiphene compared to a drop to 35% in patients who received bromocriptine. Clomiphene was also less effective than bromocriptine in suppressing lactation and symptoms of engorgement.
A study compared clomiphene 100 mg daily for 7 days (n = 10) to placebo (n = 12) started on the first day postpartum. Clomiphene was no more effective than placebo in suppressing lactation or reducing serum prolactin concentrations.
Women in the first week postpartum who did not wish to breastfeed received either clomiphene 50 mg twice daily (n = 10) or placebo (n = 10). Women who received clomiphene did not experience a rise in serum prolactin from baseline values during use of a breast pump; those given placebo had the normal post-stimulation rise in serum prolactin.
Eighty postpartum women were studied. Forty received clomiphene 50 mg twice daily for 5 days beginning the first day postpartum; 20 received clomiphene 50 mg twice daily for 5 days beginning the fourth day postpartum; and, 20 received placebo. All women receiving clomiphene experienced inhibition of lactation, and reductions in breast engorgement, discomfort and serum prolactin. Prolactin serum concentrations became statistically lower than baseline on day 3 for the women who were 1 day postpartum and on day 5 for those who were 4 days postpartum at the outset. Placebo did not suppress lactation nor suppress serum prolactin.

[1]. Differential effects of isomers of clomiphene citrate on reproductive tissues in male mice. BJU Int. 2016 Feb;117(2):344-50.

[2]. Single-dose pharmacokinetics of clomiphene citrate in normal volunteers. Fertil Steril. 1986 Sep;46(3):392-6.

[3]. Sutherland RL. Estrogen antagonists in chick oviduct: antagonist activity of eight synthetic triphenylethylene derivatives and their interactions with cytoplasmic and nuclear estrogen receptors. Endocrinology. 1981 Dec;109(6):2061-8.

[4]. The biochemical and morphological response of hydrolytic enzymes in the developing brain to hypocholesterolemic agents. Acta Neuropathol. 1980;49(2):89-94.

[5]. Discovery of High-Affinity Ligands of σ1 Receptor, ERG2, and Emopamil Binding Protein by Pharmacophore Modeling and Virtual Screening. J Med Chem. 2005 Jul 28;48(15):4754-64.

Zuclomiphene is one of the geometric isomers of clomiphene citrate, a triphenylethylene derivative. Its anti-estrogenic activity in reproductive tissues contributes to its effects on male reproductive parameters, including testis weight and sperm characteristics [1] [3]
Clomiphene Citrate can cause cancer and developmental toxicity according to state or federal government labeling requirements.
Zuclomiphene Citrate is the cis isomer of clomiphene which exhibits weak estrogen agonist activity evaluated for antineoplastic activity against breast cancer. (NCI04)
Clomiphene Citrate is the citrate salt form of clomiphene, a triphenylethylene nonsteroidal ovulatory stimulant evaluated for antineoplastic activity against breast cancer. Clomiphene has both estrogenic and anti-estrogenic activities that compete with estrogen for binding at estrogen receptor sites in target tissues. This agent causes the release of the pituitary gonadotropins follicle stimulating hormone (FSH) and luteinizing hormone (LH), leading to ovulation. (NCI04)
A triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on the target tissue. Note that ENCLOMIPHENE and ZUCLOMIPHENE are the (E) and (Z) isomers of Clomiphene respectively.
See also: Clomiphene Citrate (annotation moved to).

C₃₂H₃₆CLNO₈

598.08

597.213

7619-53-6

Zuclomiphene-d4 citrate;2714316-71-7;Zuclomiphene-d5 citrate;1795132-80-7

3033832

White to off-white solid powder

5.314

144.6

4

9

14

42

708

0

CCN(CC)CCOC1=CC=C(C=C1)/C(=C(/C2=CC=CC=C2)\Cl)/C3=CC=CC=C3.C(C(=O)O)C(CC(=O)O)(C(=O)O)O

PYTMYKVIJXPNBD-OQKDUQJOSA-N

InChI=1S/C26H28ClNO.C6H8O7/c1-3-28(4-2)19-20-29-24-17-15-22(16-18-24)25(21-11-7-5-8-12-21)26(27)23-13-9-6-10-14-23;7-3(8)1-6(13,5(11)12)2-4(9)10/h5-18H,3-4,19-20H2,1-2H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/b26-25-;

2-[4-[(Z)-2-chloro-1,2-diphenylethenyl]phenoxy]-N,N-diethylethanamine;2-hydroxypropane-1,2,3-tricarboxylic acid

Zuclomiphene citrate; Zuclomiphene citrate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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

DMSO : ~100 mg/mL (~167.20 mM)

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。