Development of steroid sulfatase inhibitors.
Hydrolysis of biologically inactive steroid sulfates to unconjugated steroids by steroid sulfatase (STS) is strongly implicated in rendering estrogenic stimulation to hormone-dependent cancers such as those of the breast. Considerable progress has been made in the past two decades with regard to the discovery, design and development of STS inhibitors. We outline historical aspects of their development, cumulating in the discovery of the first clinical trial candidate STX64 (BN83495, Irosustat) and other sulfamate-based inhibitors. The development of reversible STS inhibitors and the design of dual inhibitors of both aromatase and STS is also discussed.
Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
L W Lawrence
LW
Woo
Atul
A
Purohit
Barry V L
BV
Potter
D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004970:Estrone / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013451:Sulfonic Acids; D004970:Estrone; C005741:sulfamic acid; D043266:Steryl-Sulfatase; C017296:estrone sulfate