| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Estrone sulfatase (IC50 = 251 nM); Estrone sulfatase (Ki =133 nM)[1]
Estradiol 3-sulfamate targets steroid sulfatase (STS), an enzyme that hydrolyzes estrone sulfate to estrone. By inhibiting STS, it reduces the local production of estrogens in tissues such as breast and endometrium. It may also bind to estrogen receptors, acting as a weak estrogen agonist or antagonist. |
|---|---|
| ln Vitro |
Estrone sulfamate enzyme inhibitory activity is markedly increased by the addition of a fluorine, chlorine, or bromine moiety at the C-2 position of EMATE and estradiol 3-sulfamate, as well as by the addition of a fluorine moiety at the C-4 position of the parent sulfamate [1].
In vitro, estradiol 3-sulfamate potently inhibits STS activity in various cell lines, including breast cancer cells. It shows IC50 values in the nanomolar range. It also inhibits the growth of estrogen-dependent cancer cells by reducing estrogen levels. It may have additional effects on estrogen receptor signaling. |
| ln Vivo |
Both estradiol 3-sulfamate and its oxidative metabolite EMATE are easily absorbed and converted in the intestine, and studies have demonstrated that they are both strong, long-acting, and oral active STS inhibitors [2].
In vivo, estradiol 3-sulfamate has been shown to inhibit STS activity in animal models and reduce tumor growth in estrogen-dependent xenograft models. It has been studied in preclinical models of breast cancer and endometriosis. It has a favorable pharmacokinetic profile with good oral bioavailability. |
| Enzyme Assay |
Our rationale is based on the finding that estrone 3-sulfamate (EMATE, 2d), a typical estrone sulfatase (ES) inhibitor, can be hydrolyzed and the pharmacological effect of the free estrogen contributes to the bioactivity of the sulfamate. A number of 3-sulfamoylated derivatives of the good aromatase inhibitors, 2- and 4-halogeno (F, Cl, and Br) estrones and their estradiol analogs as well as 6beta-methyl and phenyl estrones, were synthesized and evaluated as inhibitors of ES in human placental microsomes in comparison with the lead compound EMATE. Among them, 2-chloro- and 2-bromoestrone 3-sulfamates (2b and 2c), along with their estradiol analogs 3b and 3c, were powerful competitive inhibitors with K(i)'s ranging between 4.0 and 11.3 nM (K(i) for EMATE, 73 nM). These four sulfamates as well as the 2-fluoro analogs 2a and 3a inactivated ES in a time-dependent manner more efficiently than EMATE, and 2-halogeno estrone sulfamates 2 also caused a concentration-dependent loss of ES activity. The results may be useful for developing a new class of drugs having a dual function, ES inhibition and aromatase inhibition, for the treatment of breast cancer[1].
STS activity is measured using radiolabeled estrone sulfate as a substrate. Tissue homogenates or cell lysates are incubated with the substrate and various concentrations of estradiol 3-sulfamate. The production of estrone is quantified by scintillation counting after separation by chromatography. IC50 values are calculated from dose-response curves. |
| Cell Assay |
Breast cancer cell lines (e.g., MCF-7) are cultured and treated with estradiol 3-sulfamate. Cell proliferation is assessed by MTT assay or by measuring [3H]-thymidine incorporation. Estrogen levels in the culture medium are measured by ELISA. STS activity in cell lysates is measured as described above.
|
| Animal Protocol |
The combination of a progestin such as norethindrone acetate (NETA) reducing the ovarian estrogen production with a steroid sulfatase (STS) inhibitor (STS-I) decreasing the local estrogen production could result in a new treatment option for endometriosis. The study reported was a randomized, double-blind, and placebo-controlled study to investigate the pharmacodynamics, pharmacokinetics, and safety of the STS-I PGL2001 (E2MATE) and NETA. A total of 24 healthy women of reproductive age were treated with weekly doses of PGL2001 or daily doses of NETA or a combination of both compounds for 4 weeks. Four weeks of treatment with PGL2001 or PGL2001 + NETA reduced the STS activity in the endometrium by 91% (±3%) and 96% (±4%), respectively, and comparable values were observed 1 month after the treatment was stopped. The combined treatment of PGL2001 + NETA led to significantly higher STS inhibition at both times (P < .01 and P < .05, respectively). This study showed that administration of PGL2001 alone at 4 mg/week or combined with NETA to healthy women of reproductive age led to STS inhibition and changes in functional STS biomarkers in the endometrium, resulting in synergistic effects of PGL2001 and NETA on STS activity[2].
Animal models include nude mice bearing MCF-7 xenograft tumors. Estradiol 3-sulfamate is administered orally or subcutaneously. Tumor volume is measured over time. STS activity and estrogen levels are measured in tumor tissues. Pharmacokinetic parameters are assessed by blood sampling. |
| ADME/Pharmacokinetics |
Estradiol 3-sulfamate (MW 349.44) is a small molecule with good oral bioavailability. It is metabolized in the liver and excreted in urine and bile. Its half-life is several hours. It has been shown to have a favorable pharmacokinetic profile in preclinical studies.
|
| Toxicity/Toxicokinetics |
Estradiol 3-sulfamate has been shown to have a good safety profile in preclinical studies. No significant toxicity has been reported at pharmacologically active doses. It is not associated with the estrogenic side effects of estradiol, as it acts primarily as an STS inhibitor.
|
| References |
|
| Additional Infomation |
Drug Indication
This drug has been studied for the treatment of endometriosis. Estradiol 3-sulfamate (BLE 00084) is an investigational drug being developed for the treatment of estrogen-dependent cancers. It has been studied in preclinical models and early clinical trials. It is not yet approved for clinical use. It is used as a research tool to study STS inhibition and estrogen metabolism. |
| Molecular Formula |
C18H25NO4S
|
|---|---|
| Molecular Weight |
351.4604
|
| Exact Mass |
351.15042
|
| Elemental Analysis |
C, 61.51; H, 7.17; N, 3.99; O, 18.21; S, 9.12
|
| CAS # |
172377-52-5
|
| Related CAS # |
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 |
6918339
|
| Appearance |
White to off-white solid powder
|
| LogP |
1.9
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
24
|
| Complexity |
588
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
S(N([H])[H])(=O)(=O)OC1C([H])=C([H])C2=C(C=1[H])C([H])([H])C([H])([H])C1([H])C2([H])C([H])([H])C([H])([H])C2(C([H])([H])[H])C([H])(C([H])([H])C([H])([H])C21[H])O[H]
|
| InChi Key |
YXYXCSOJKUAPJI-ZBRFXRBCSA-N
|
| InChi Code |
InChI=1S/C18H25NO4S/c1-18-9-8-14-13-5-3-12(23-24(19,21)22)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,20H,2,4,6-9H2,1H3,(H2,19,21,22)/t14-,15-,16+,17+,18+/m1/s1
|
| Chemical Name |
[(8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl] sulfamate
|
| Synonyms |
Estradiol 3-sulfamate; estradiol sulfamate; 172377-52-5; E2MATE; Estradiol-3-O-sulfamate; J-995; WO55ODW08Z; PGL2001;
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~177.83 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.92 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 20.8 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: ≥ 2.08 mg/mL (5.92 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8453 mL | 14.2264 mL | 28.4527 mL | |
| 5 mM | 0.5691 mL | 2.8453 mL | 5.6905 mL | |
| 10 mM | 0.2845 mL | 1.4226 mL | 2.8453 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
