After stably transfecting T47D cells with SOAT, the cells were cultured at physiologically relevant amounts of estradiol and estrone sulfate. With an EC50 of 2.2 nM, 1 nM estradiol and esttrone sulfate markedly enhanced cell proliferation [3].

Absorption, Distribution and Excretion
Conjugated estrogens are well absorbed in the gastrointestinal tract. Peak plasma concentrations are reached after 7 hours, depending on the estrone component. It has been reported that after multiple doses of 0.45 mg, the peak plasma concentration of conjugated estrogens is 2.6 ng/ml, with a steady-state AUC of 35 ng·h/ml. Unconjugated estrogens are known to be cleared from circulation faster than their esterified forms. Conjugated estrogens are primarily excreted in the urine. During renal excretion, 17β-estradiol, estrone, estriol, and glucuronide and sulfate conjugates of estrogen can be detected. The physiological distribution of estrogens in the body is very similar to that of endogenous estrogens, and therefore they are widely distributed. Conjugated estrogens are primarily found in the target organs of sex hormones. The normal clearance rate of estrogen has been reported to be approximately 615 L/m². Metabolism/Metabolites Conjugated estrogens are metabolized through several different pathways. One metabolic pathway is driven by the action of the cytochrome isoenzyme CYP3A4. Conjugated estrogens, on the other hand, can also be processed through a dynamic balance of metabolic transformation and sulfate conjugation. Some of the major metabolic reactions of conjugated estrogens are driven by the conversion of 17β-estradiol to estrone and further to estriol. A portion of ingested conjugated estrogens remains in the blood as sulfate conjugates, serving as a circulating reservoir for the generation of new estrogens. In the endometrium, equine estrogens are metabolized to 2-hydroxyequine estrogens and 4-hydroxyequine estrogens, as well as 2-hydroxyestradiol and 4-hydroxyestradiol. This hydroxylation process is very common in various components of conjugated estrogens; therefore, the major metabolites in urine are known to be 17-ketosteroid-16-α-hydroxyestradiol, 16-α-hydroxy-17-β-dihydroequinophenone, and 16-α-hydroxy-17-β-dihydroequinophenone.

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Biological Half-Life
The median half-life of conjugated estrogens has been reported to be 17 hours.

Protein Binding
Estrogen binds to plasma proteins, and this binding state can account for approximately 50-80% of the administered dose. It mainly binds to sex hormone-binding globulins and albumin, circulating in the bloodstream.

[1]. Steroid sulfatase and estrogen sulfotransferase in the atherosclerotic human aorta. Am J Pathol. 2003;163(4):1329-1339.

[2]. Inhibition of estrone sulfatase activity by estrone-3-methylthiophosphonate: a potential therapeutic agent in breast cancer. Cancer Res. 1993;53(2):298-303.

[3]. Estrone-3-Sulfate Stimulates the Proliferation of T47D Breast Cancer Cells Stably Transfected With the Sodium-Dependent Organic Anion Transporter SOAT (SLC10A6). Front Pharmacol. 2018;9:941. Published 2018 Aug 21.

Sodium estrone sulfate is a steroidal sulfate and organic sodium salt whose function is related to estrone. Conjugated estrogens are noncrystalline mixtures of purified estrogens obtained from either the urine of pregnant mares or from plant material. Both products are then bound to sodium sulfate via ester bonds to improve their water solubility. Conjugated estrogens contain multiple estrogens, approximately 50% estrone sulfate, followed by 25% malrenone sulfate, 15% 17α-dehydromalrenone sulfate, 3% malrenone sulfate, 5% 17α and 17β-dihydromalrenone sulfate, 2% 17α-estradiol sulfate, and 3% 17β-estradiol sulfate. The conjugated estrogens mixture extracted from the urine of pregnant mares also contains a large number of unidentified molecules with weak estrogenic activity and non-human molecules. This conjugated estrogens mixture was approved for marketing in the United States in 1942 based on its efficacy against certain diseases. However, formal clinical trials were not conducted until 1986, confirming the product's effectiveness in treating osteoporosis. Currently approved conjugated estrogen products were developed by Wyeth Ayerst and received FDA approval in 2003.

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Drug Indications
Conjugated estrogen is indicated for a variety of conditions, including: - Treatment of moderate to severe menopausal vasomotor symptoms. - Treatment of moderate to severe menopausal vulvar and vaginal atrophy symptoms. - Treatment of low estrogen levels due to hypogonadism, castration, or primary ovarian failure. - Palliative care for appropriately screened patients with metastatic breast cancer. - Relief of symptoms in androgen-dependent prostate cancer. - Prevention of postmenopausal osteoporosis.
FDA LabelMechanism of Action
Conjugated estrogen, like normal physiological estrogen, works by agonizing the binding of estrogen receptors α and β. The number and proportion of estrogen receptors vary from tissue to tissue, resulting in significant differences in the activity of bound estrogen. The activity of bound estrogen is driven by increased synthesis of DNA, RNA, and various proteins in the responding tissue, which in turn reduces the release of gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone. The specific mechanism of action cannot be described solely by the total estrogenic effect, as the pharmacokinetic characteristics, tissue specificity, and tissue metabolism of each component of the product differ.

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Pharmacodynamics
After binding to estrogen receptors, estrogen activates nuclear receptors, which in turn bind to estrogen-responsive elements in certain target genes. This cascade of mechanisms leads to histone acetylation, chromatin conformational changes, and the initiation of transcription for certain drugs. Preclinical studies have shown that the estrogenic potency of bound estrogen is similar to that of estrone, and the masenoyl component of bound estrogen has similar potency in the liver to its biocompatible estradiol. Furthermore, bound estrogen has been shown to possess selective estrogen receptor modulator properties, resulting in significant benefits for the skeletal and cardiovascular systems. Clinically, it is known that administration of conjugated estrogen can promote vasomotor stability, maintain urogenital function, and promote the normal growth and development of female sex hormones. Furthermore, it can prevent accelerated bone loss by inhibiting bone resorption and restoring bone resorption balance. Hormonally, it can also inhibit luteinizing hormone and lower serum testosterone levels.

C18H21O5S-.NA+

372.41114

372.1

C, 58.05; H, 5.68; Na, 6.17; O, 21.48; S, 8.61

438-67-5

481-97-0 (free acid);438-67-5 (sodium);

23667301

White to off-white solid powder

1.349 g/cm3

258-260°C

4.031

0

5

2

25

630

4

[Na+].O=S(OC1C=CC2[C@H]3CC[C@@]4(C(CC[C@H]4[C@@H]3CCC=2C=1)=O)C)(=O)[O-]

VUCAHVBMSFIGAI-ZFINNJDLSA-M

InChI=1S/C18H22O5S.Na/c1-18-9-8-14-13-5-3-12(23-24(20,21)22)10-11(13)2-4-15(14)16(18)6-7-17(18)19;/h3,5,10,14-16H,2,4,6-9H2,1H3,(H,20,21,22);/q;+1/p-1/t14-,15-,16+,18+;/m1./s1

sodium;[(8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfate

Estrone sulfate sodium salt; Conestoral; Estrone sodium sulfate; Estrone sulfate sodium; Morestin; NSC 18313; Sodium estrone sulfate; Sodium estrone-3-sulfate;

2934.99.9001

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.

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

DMSO : ~25 mg/mL (~67.13 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.71 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.71 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.71 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.

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 (Please use freshly prepared in vivo formulations for optimal results.)