Human Endogenous Metabolite

Endogenous metabolites are those that the Kyoto Encyclopedia of Genes and Genomes has identified as products or substrates of the approximately 1900 metabolic enzymes that are encoded in human genome. Numerous of these metabolites have been shown to have harmful effects, as evidenced by the body of literature [1].

Absorption, Distribution and Excretion
Estradiol valerate is readily absorbed through the skin and gastrointestinal tract. When applied topically, the amount absorbed is usually sufficient to produce systemic effects. Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates. Metabolism/Metabolites Exogenous estrogens are metabolized in the same way as endogenous estrogens. Circulating estrogens are in a dynamic equilibrium of metabolic interconversions. These conversions primarily occur in the liver. Estradiol is reversibly converted to estrone, and both can be converted to estriol, which is the main urinary metabolite. Estrogens also undergo enterohepatic circulation via sulfate and glucuronide conjugates in the liver. These conjugates are secreted into the intestine via bile and are hydrolyzed and reabsorbed in the intestine. In postmenopausal women, a significant portion of circulating estrogens exists in the form of sulfate conjugates, especially estrone sulfate, which serves as a circulating reserve for the synthesis of more potent estrogens.

[1]. Endogenous toxic metabolites and implications in cancer therapy. Oncogene. 2020 Aug;39(35):5709-5720.

[2]. Abnormal androgen and oestrogen metabolism in men with steroid sulphatase deficiency and recessive X-linked ichthyosis. Clin Endocrinol (Oxf). 1985 Oct;23(4):385-93.

[3]. Obese men have elevated plasma levels of estrone sulfate. Int J Obes. 1990 Jun;14(6):483-6.

Estrone-3-sulfate is a steroidal sulfate, a 3-sulfate derivative of estrone. It is a metabolite in both humans and mice. It is a 17-oxosteroid and also a steroidal sulfate. Functionally, it is related to estrone. It is the conjugate acid of estrone-3-sulfate (1-). It is derived from the hydride of estane. Estrone sulfate (in the form of estronepiperate) is a form of estrogen. It has various uses, such as: as hormone replacement therapy to relieve menopausal symptoms; treatment of certain types of infertility; treatment of certain diseases leading to incomplete development of female sexual characteristics; treatment of vaginal atrophy; treatment of certain types of breast cancer (especially in men and postmenopausal women); treatment of prostate cancer; and prevention of osteoporosis. Estrone sulfate has been reported in both Homo sapiens and common beans, and relevant data exist. Estrone sulfate is an aqueous solution and is the sulfate form of estrone. (NCI)

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Drug Indications
Estradiol is used to treat moderate to severe vasomotor symptoms associated with unilateral menopause, and moderate to severe vulvar and vaginal atrophy associated with menopause. It is also used to treat hypogonadism, castration, or primary ovarian failure leading to low estrogen levels, and to prevent postmenopausal osteoporosis.

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Mechanism of Action
Estradiol can freely enter target cells (e.g., female organs, breasts, hypothalamus, pituitary gland) and interact with target cell receptors. Once the estrogen receptor binds to its ligand, it enters the target cell nucleus, regulating gene transcription to form messenger RNA (mRNA). The mRNA interacts with ribosomes to produce specific proteins that express the effects of estradiol on target cells. Estrogen increases the synthesis of sex hormone-binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins in the liver, and inhibits the secretion of follicle-stimulating hormone (FSH) from the anterior pituitary gland.

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Pharmacodynamics
Estradiol valerate is an estrogen-like substance that acts similarly to natural estrogens. Estrogens exert their effects by binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogen regulates the pituitary gland's secretion of gonadotropins, including luteinizing hormone (LH) and follicle-stimulating hormone (FSH), through a negative feedback mechanism. Estrogen can reduce the elevated levels of these hormones in postmenopausal women.

C18H22O5S

350.43

349.111

481-97-0

Estrone sulfate potassium;1240-04-6;Estrone sulfate sodium;438-67-5

3001028

Typically exists as solid at room temperature

254.5 °C

4.031

1

5

2

24

624

4

OS(OC1C=CC2[C@@H]3CC[C@]4(C(CC[C@@H]4[C@H]3CCC=2C=1)=O)C)(=O)=O

JKKFKPJIXZFSSB-CBZIJGRNSA-N

InChI=1S/C18H22O5S/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)/t14-,15-,16+,18+/m1/s1

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

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

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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