Inhibitors of 17β-hydroxysteroid dehydrogenase type 1, 2 and 14: Structures, biological activities and future challenges

During the past 25 years, the modulation of estrogen action by inhibition of 17 beta-hydroxysteroid dehydrogenase types 1 and 2 (17 beta-HSD1 and 17 beta-HSD2), respectively, has been pursued intensively. In the search for novel treatment options for estrogen-dependent diseases (EDD) and in order to explore estrogenic signaling pathways, a large number of steroidal and nonsteroidal inhibitors of these enzymes has been described in the literature. The present review gives a survey on the development of inhibitor classes as well as the structural formulas and biological properties of their most interesting representatives. In addition, rationally designed dual inhibitors of both 17 beta-HSD1 and steroid sulfatase (STS) as well as the first inhibitors of 17 beta-HSD14 are covered.