Recent advances in the development of 17beta-hydroxysteroid dehydrogenase inhibitors

Abstract

The family of 17β-hydroxysteroid dehydrogenases (17β-HSDs) occupies a prominent place due to its number of isoforms, which carry out a bidirectional transformation (reduction of a steroid carbonyl to alcohol and oxidation of a steroid alcohol to ketone) depending on the nature of the cofactor present. Involved in the activation or inactivation of key estrogens and androgens, 17β-HSDs are therefore therapeutic targets whose selective inhibition would make it possible to be considered for the treatment of several diseases, such as breast cancer, prostate cancer, endometriosis, Alzheimer’s disease and osteoporosis. This review article is a continuation of those having reported the great diversity of inhibitors developed over the last years but focusses on inhibitors recently developed. Work to obtain more effective inhibitors that target the first known isoforms (types 1, 2, 3, 5 and 7) has continued, among others, but new inhibitors that target the isoforms more recently reported in the literature (types 10, 12, 13 and 14) are now being reported. Dual inhibitors of two enzymes (17β-HSD1 and steroid sulfatase) were also reported. These inhibitors were grouped according to the 17β-HSD type inhibited and their backbone (steroidal or non-steroidal) when necessary. They were also reported in chronological order and according to the research group.