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.
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