Estradiol sulfamate (E2MATE; developmental code names J995, PGL-2, PGL-2001, ZK-190628, others), or estradiol-3-O-sulfamate, is a steroid sulfatase (STS) inhibitor which is under development for the treatment of endometriosis.

Such aryl sulfamate esters were shown to be "first-in-class" highly potent active site-directed irreversible STS inhibitors.

[8][12] As a result, EMATE prevents the bioactivation of itself and E2MATE into estrone and estradiol, respectively, which effectively abolishes their estrogenic activity in humans.

STS inhibition in the human was probably the mechanism for very long lasting high [E2MATE]- and EMATE concentrations in erythrocytes compared to shorter initial peak values of [estrone] and [estradiol] in the plasma.

"[8] As such, E2MATE and EMATE are not effective as estrogens in humans, and the researchers have subsequently developed new C17β sulfonamide ester prodrugs of estradiol, such as EC508, that cannot be transformed into the corresponding estrone equivalents and are not STS inhibitors.

[4] In a clinical study, E2MATE was found to inhibit endometrial STS activity by 91% in premenopausal women, while circulating levels of estradiol were not affected, indicating that E2MATE may have tissue-selective antiestrogenic effects in the endometrium.

[1] EMATE and E2MATE are almost completely sequestered into erythrocytes from the hepatic portal vein during the first pass with oral administration, thereby bypassing the liver.

[1] Treatment with 4 mg oral E2MATE once per week has been found to result in very high maximal levels of E2MATE of 152.1 ng/mL (152,100 pg/mL) and of EMATE of 2,395 ng/mL (2,395,000 pg/mL) in women.