Estradiol 3-sulfamate (BLE 00084; E2MATE; ES-J 995) is a long-acting and orally bioactive steroid sulfatase inhibitor; the IC50 for inhibiting estrone sulfatase is 251 nM, Ki The value is 133 nM.

Physicochemical Properties

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)

Biological Activity

Targets	Estrone sulfatase (IC50 = 251 nM); Estrone sulfatase (Ki =133 nM)[1]
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].
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].
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].
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].
References	[1]. Inhibition of estrone sulfatase by aromatase inhibitor-based estrogen 3-sulfamates. Steroids. 2006 May;71(5):371-9. [2]. Synergistic effects of E2MATE and norethindrone acetate on steroid sulfatase inhibition: a randomized phase I proof-of-principle clinical study in women of reproductive age. Reprod Sci. 2014 Oct;21(10):1256-65.
Additional Infomation	Drug Indication Investigated for use/treatment in endometriosis.

Solubility Data

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. 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. 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 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	2.8453 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.