Abstract
Estrogen sulfamate derivatives were the first irreversible active-site-directed inhibitors of steroid sulfatase (STS), an emerging drug target for endocrine therapy of hormone dependent diseases that catalyzes inter alia the hydrolysis of estrone sulfate to estrone. In recent years this has stimulated clinical investigation of the estradiol derivative both as an oral prodrug and its currently ongoing exploration in endometriosis. 2-Substituted steroid sulfamate derivatives show considerable potential as multi-targeting agents for hormone-independent disease, but are also potent STS inhibitors. The steroidal template has spawned nonsteroidal STS inhibitors one of which, Irosustat, has been evaluated clinically in breast cancer, endometrial cancer and prostate cancer and there is potential for innovative dual-targeting approaches. This review surveys the role of estrogen sulfamates, their analogues and current status.
| Original language | English |
|---|---|
| Article number | 4391 |
| Pages (from-to) | 160-169 |
| Number of pages | 10 |
| Journal | Journal of Steroid Biochemistry and Molecular Biology |
| Volume | 153 |
| Early online date | 2 Apr 2015 |
| DOIs | |
| Publication status | Published - 1 Sep 2015 |
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Keywords
- Cancer
- Endocrine Therapy
- Inhibitor
- Sulfamates
- Sulfatase
- Synthesis
Cite this
Estrogen O-sulfamates and their analogues : clinical steroid sulfatase inhibitors with broad potential. / Thomas, Mark P.; Potter, Barry V. L.
In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 153, 4391, 01.09.2015, p. 160-169.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Estrogen O-sulfamates and their analogues
T2 - clinical steroid sulfatase inhibitors with broad potential
AU - Thomas, Mark P.
AU - Potter, Barry V. L.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Estrogen sulfamate derivatives were the first irreversible active-site-directed inhibitors of steroid sulfatase (STS), an emerging drug target for endocrine therapy of hormone dependent diseases that catalyzes inter alia the hydrolysis of estrone sulfate to estrone. In recent years this has stimulated clinical investigation of the estradiol derivative both as an oral prodrug and its currently ongoing exploration in endometriosis. 2-Substituted steroid sulfamate derivatives show considerable potential as multi-targeting agents for hormone-independent disease, but are also potent STS inhibitors. The steroidal template has spawned nonsteroidal STS inhibitors one of which, Irosustat, has been evaluated clinically in breast cancer, endometrial cancer and prostate cancer and there is potential for innovative dual-targeting approaches. This review surveys the role of estrogen sulfamates, their analogues and current status.
AB - Estrogen sulfamate derivatives were the first irreversible active-site-directed inhibitors of steroid sulfatase (STS), an emerging drug target for endocrine therapy of hormone dependent diseases that catalyzes inter alia the hydrolysis of estrone sulfate to estrone. In recent years this has stimulated clinical investigation of the estradiol derivative both as an oral prodrug and its currently ongoing exploration in endometriosis. 2-Substituted steroid sulfamate derivatives show considerable potential as multi-targeting agents for hormone-independent disease, but are also potent STS inhibitors. The steroidal template has spawned nonsteroidal STS inhibitors one of which, Irosustat, has been evaluated clinically in breast cancer, endometrial cancer and prostate cancer and there is potential for innovative dual-targeting approaches. This review surveys the role of estrogen sulfamates, their analogues and current status.
KW - Cancer
KW - Endocrine Therapy
KW - Inhibitor
KW - Sulfamates
KW - Sulfatase
KW - Synthesis
UR - http://www.scopus.com/inward/record.url?scp=84941260021&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1016/j.jsbmb.2015.03.012
U2 - 10.1016/j.jsbmb.2015.03.012
DO - 10.1016/j.jsbmb.2015.03.012
M3 - Article
VL - 153
SP - 160
EP - 169
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
M1 - 4391
ER -