The 17β-hydroxysteroid dehydrogenases (17β-HSDs) play an important role in the regulation of steroid hormones, such as estrogens and androgens, by catalysing the reduction of 17-ketosteroids or the oxidation of 17β-hydroxysteroids using NAD(P)H or NAD(P)+ as cofactor. The enzyme activities associated with the different 17β-HSD isoforms are widespread in human tissues, not only in classic steroidogenic tissues, such as the testis, ovary, and placenta, but also in a large series of peripheral intracrine tissues. In the nineties, several new types of 17β-HSD were reported, indicating that a fine regulation is carried out. More importantly, each type of 17β-HSD has a selective substrate affinity, directional (reductive or oxidative) activity in intact cells, and a particular tissue distribution. These findings are important for understanding the mode of action of the 17β-HSD family. From a therapeutic point of view, this means that selectivity of drug action could be achieved by targeting a particular 17β-HSD isozyme. Consequently, each study that leads to better knowledge of the inhibition of 17β-HSDs deserves attention from scientists working in this and related fields. Being involved in the last step of the biosynthesis of sex steroids from cholesterol, the 17β-HSD family constitutes an interesting target for controlling the concentration of estrogens and androgens. Thus, inhibitors of 17β-HSDs are useful tools to elucidate the role of these enzymes in particular biological systems or for a therapeutic purpose, especially to block the formation of active hydroxysteroids that stimulate estrogeno-sensitive pathologies (breast, ovarian, and endometrium cancers) and androgeno-sensitive pathologies (prostate cancer, benign prostatic hyperplasia, acne, hirsutism, etc). Few review articles have however focussed on 17β-HSD inhibitors although this family of steroidogenic enzymes includes interesting therapeutic targets for the control of several diseases. Furthermore, inhibitors of 17β-HSDs constitute a growing field in biomedical research and there is a need for an exhaustive review on this topic. In addition to giving an up-to-date description of inhibitors of all 17β-HSD isoforms (types 1-8), the present review will also address, when possible, the isoform selectivity and residual estrogenic or androgenic activity often associated with steroidal inhibitors.

17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) mainly catalyze the reduction of C17-ketosteroids to their corresponding hydroxylated forms as well as the reverse reaction (oxidation). Able to convert inactive or less active steroid hormones into more potent ones and vice versa, certain 17beta-HSDs play a key role, especially in the regulation of estrogen and androgen levels. The therapeutic potential of this enzyme family, especially for the treatment of breast cancer, prostate cancer, acne and osteoporosis, then stimulated the development of inhibitors of 17beta-HSDs and important progress was achieved over the last years. This review article reports all patent applications related to the inhibitors of 17beta-HSDs, including some articles needed to complement the information presented. Readers will be informed about the role and function of 17beta-HSDs in the first section and about the history of inhibitor development in the second section. Furthermore, in the third and main section, the readers will learn about the structures of patented inhibitors originating from different companies and academic groups. The increase in the number of 17beta-HSD inhibitors reported in the last years augurs well for the future. The challenge is now to translate these results into clinical studies to allow determination of the therapeutic usefulness of 17beta-HSD inhibitors.

The 17β-hydroxysteroid dehydrogenases (17β-HSDs) are involved in the regulation of estrogens and androgens by catalyzing the reduction of 17-ketosteroids or the oxidation of 17β-hydroxysteroids. The enzyme activities associated with the different 17β-HSD isoforms are widespread in human tissues, not only in classic steroidogenic tissues but also in a large series of peripheral intracrine tissues. Being involved at the end of steroidogenesis, the numerous members of 17β-HSD family constitute interesting therapeutic targets for controlling the concentration of estrogens and androgens. Thus, inhibitors of reductive 17β-HSD isoforms are attractive to block the formation of hydroxysteroids that stimulate estrogeno-sensitive pathologies (breast, ovarian, and endometrium cancers) and androgenosensitive pathologies (prostate cancer, benign prostatic hyperplasia, acne, and hirsutism). The inhibitors could be used to block the degradation of estradiol, an attractive strategy for treating osteoporosis and Alzheimers disease. In addition to their classical use as anti-cancer agents and therapeutic agents, inhibitors of 17β-HSDs are also useful tools to elucidate the role of these enzymes in particular biological systems. The present review article gives a description of novel inhibitors of 17β-HSDs that were published in 2003-2006.