 Chemical Structure.png)
Estradiol cypionate (Depoestradiol; β-Estradiol 17-cypionate) is the 17 β-cyclopentylpropinate ester of estradiol used in hormone therapy for menopausal symptoms and low estrogen levels in women. It acts by inhibiting ET-1 synthesis via estrogen receptor. Estradiol cypionate is a synthetic ester of the natural estrogen, estradiol. Compared to other commonly used estradiol esters, via the intramuscular route, estradiol cypionate is found to have the longest duration of action with a duration of ~11 days, while estradiol benzoate and estradiol valerate are found to last for 4-5 days and 7-8 days, respectively.
Physicochemical Properties
| Molecular Formula | C26H36O3 | |
| Molecular Weight | 396.56 | |
| Exact Mass | 396.266 | |
| Elemental Analysis | C, 78.75; H, 9.15; O, 12.10 | |
| CAS # | 313-06-4 | |
| Related CAS # | Estradiol;50-28-2;Estradiol benzoate;50-50-0;Estradiol enanthate;4956-37-0; Alpha-Estradiol;57-91-0;Estradiol (Standard);50-28-2;Estradiol-d3;79037-37-9;Estradiol-d4;66789-03-5;Estradiol-d5;221093-45-4;Estradiol-13C2;82938-05-4;Estradiol (cypionate);313-06-4;Estradiol benzoate;50-50-0;Estradiol enanthate;4956-37-0;Estradiol hemihydrate;35380-71-3;Estradiol-d2;53866-33-4;Estradiol-13C6;Estradiol-d2-1;3188-46-3;rel-Estradiol-13C6; 979-32-8 (valerate); 113-38-2 (dipropionate); 57-63-6 (ethinyl); 172377-52-5 (sulfamate); 3571-53-7 (undecylate) | |
| PubChem CID | 9403 | |
| Appearance | White to off-white solid powder | |
| Density | 1.2±0.1 g/cm3 | |
| Boiling Point | 532.8±50.0 °C at 760 mmHg | |
| Melting Point | ≥300 °C(lit.) | |
| Flash Point | 207.7±22.9 °C | |
| Vapour Pressure | 0.0±1.5 mmHg at 25°C | |
| Index of Refraction | 1.579 | |
| LogP | 7.59 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 3 | |
| Rotatable Bond Count | 5 | |
| Heavy Atom Count | 29 | |
| Complexity | 597 | |
| Defined Atom Stereocenter Count | 5 | |
| SMILES | C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2OC(=O)CCC4CCCC4)CCC5=C3C=CC(=C5)O |
|
| InChi Key | UOACKFBJUYNSLK-XRKIENNPSA-N | |
| InChi Code | InChI=1S/C26H36O3/c1-26-15-14-21-20-10-8-19(27)16-18(20)7-9-22(21)23(26)11-12-24(26)29-25(28)13-6-17-4-2-3-5-17/h8,10,16-17,21-24,27H,2-7,9,11-15H2,1H3/t21-,22-,23+,24+,26+/m1/s1 | |
| Chemical Name | Cyclopentanepropionic acid, 3-hydroxyestra-1,3,5(10)-trien-17beta-yl ester | |
| Synonyms |
|
|
| 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: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
|
| 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
| Targets | ER |
| ln Vitro | Gastric cancer cells (MGC803, SGC7901, and BGC823) are not able to proliferate when exposed to estradiol cypionate (0-30 μM) for a period of 72 hours [4]. In the G1/S phase of gastric cancer cells (MGC803, SGC7901, and BGC823 cells), estradiol cypionate (10–25 μM) can cause cell cycle arrest and trigger apoptosis via the PI3K/Akt/mTOR pathway [4]. |
| ln Vivo | In adolescent ovariectomized (OVX) rabbits, cortical bone density is increased by weekly intramuscular injections of estradiol cypionate (70 μg/kg) [2]. In dairy cows, the intramuscular injection of 1 mg of estradiol cypionate increases the incidence of estrus and pregnancy [3]. Estradiol cypionate (50-100mg/kg, intraperitoneal injection, every other day) inhibits tumor growth in MGC803 nude mice [4]. |
| Enzyme Assay | Estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating AKT ubiquitination: Gastric cancer is a common gastrointestinal malignancy worldwide, with a high mortality rate and poor prognosis. Multidrug resistance remains a major obstacle to successful treatment for patients. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect. In this study, we have investigated the effect of estradiol cypionate (ECP) on gastric cancer in vitro and vivo. Our data show that ECP inhibited the proliferation, promoted apoptosis, and caused G1/S phase arrest of gastric cancer cells. The mechanism by which ECP promoted apoptosis of gastric cancer cells was related to the downregulation of AKT protein expression caused by the increased ubiquitination modification levels of AKT, which finally inhibited the over-activation of the PI3K-AKT-mTOR signaling pathway. In vivo tumorigenesis experiments showed that ECP significantly inhibited the growth of gastric cancer cells, showing promise for clinical application. The above findings indicate that ECP inhibited the growth of gastric cancer and induced apoptosis through the PI3K /Akt/mTOR pathway. In summary, the efficacy showed in our data suggests that ECP is a promising anti-tumor compound for gastric cancer[4]. |
| Cell Assay |
Western Blot Analysis[4] Cell Types: MGC803, SGC7901, and BGC823 cells Tested Concentrations: 10-25 μM Incubation Duration: 48 h Experimental Results: Increased protein level of cleaved caspase-3 and PARP. diminished protein levels of AKT, p-AKT, p-mTOR, p-S6K, and p-4E-BP1. |
| Animal Protocol |
Animal/Disease Models: MGC803 nude mice tumor model[4]. Doses: 50-100 mg/kg Route of Administration: ip, every other day Experimental Results: Inhibited tumor growth. Increased Cleaved caspase-3 expression, diminished Ki67, AKT and p-AKT in tumors . |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion When conjugated with aryl and alkyl groups for parenteral administration, the rate of absorption of oily preparations is slowed with a prolonged duration of action, such that a single intramuscular injection of estradiol valerate or estradiol cypionate is absorbed over several weeks. Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates. The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. Metabolism / Metabolites Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Estradiol cypionate has not been studied during breastfeeding. However, a similar drug, estradiol valerate, has been used to suppress lactation, usually in combination with testosterone. Generally, estradiol cypionate should be avoided in mothers wishing to breastfeed, especially if started before the milk supply is well established at about 6 weeks postpartum. The decrease in milk supply can happen over the first few days of estrogen exposure. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Another injection ester form of estradiol, estradiol valerate was previously used therapeutically to suppress lactation, usually in combination with testosterone. A retrospective cohort study compared 371 women who received high-dose estrogen (either 3 mg of diethylstilbestrol or 150 mcg of ethinyl estradiol daily) during adolescence for adult height reduction to 409 women who did not receive estrogen. No difference in breastfeeding duration was found between the two groups, indicating that high-dose estrogen during adolescence has no effect on later breastfeeding. Protein Binding Estrogens circulate in the blood largely bound to sex hormone binding globulin (SHBG) and albumin. |
| References |
[1]. NMI inhibits cancer stem cell traits by downregulating hTERT in breast cancer. Cell Death Dis. 2017 May 11;8(5):e2783. [2]. Resveratrol treatment delays growth plate fusion and improves bone growth in female rabbits. PLoS One. 2013 Jun 28;8(6):e67859. [3]. Impact of hormonal modulation at proestrus on ovarian responses and uterine gene expression of suckled anestrous beef cows. J Anim Sci Biotechnol. 2017 Nov 1;8:79. [4]. Estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating AKT ubiquitination. Biomed Pharmacother. 2023 Sep;165:115073. |
| Additional Infomation |
Pharmacodynamics Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular effects. |
Solubility Data
| Solubility (In Vitro) |
|
|||
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.67 mg/mL (6.73 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 26.7 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: ≥ 2.67 mg/mL (6.73 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 26.7 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 | 2.5217 mL | 12.6084 mL | 25.2169 mL | |
| 5 mM | 0.5043 mL | 2.5217 mL | 5.0434 mL | |
| 10 mM | 0.2522 mL | 1.2608 mL | 2.5217 mL |