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Inhibitors of 17[beta]-hydroxysteroid dehydrogenase type 1
Brožič, Petra ; Lanišnik-Rižner, Tea ; Gobec, Stanislav, 1970-
Carcinogenesis of hormone-related cancers involves hormone-stimulated cell proliferation, which increases the number of cell divisions and the opportunity for random genetic errors. In target ...tissues, steroid hormones areinterconverted between their potent, high affinity forms for their respective receptors and their inactive, low affinity forms. One group of enzymes responsible for these interconversions are the hydroxysteroid dehydrogenases, which regulate ligand access to steroid receptors and thus actat a pre-receptor level. As part of this group, the 17[beta]-hydroxysteroid dehydrogenases catalyze either oxidation of hydroxyl groups or reduction of keto groups at steroid position C17. The thoroughly characterized 17beta-hydroxysteroid dehydrogenase type 1 activates the less active estrone to estradiol, a potent ligand for estrogen receptors. This isoform is expressed in gonads, where it affects circulating levels of estradiol, and in peripheraltissue, where it regulates ligand occupancy of estrogen receptors. Inhibitors of 17[beta]-hydroxysteroid dehydrogenase type 1 are thus highly interesting potential therapeutic agents for the control of estrogen-dependentdiseases such as endometriosis, as well as breast and ovarian cancers. Here, we present the review on the recent development of inhibitors of 17-hydroxysteroid dehydrogenase type 1 published and patented since the previous review of 17beta-hydroxysteroid dehydrogenase inhibitors of Poirier (Curr. Med. Chem., 2003, 10, 453). These inhibitors are divided into two separate groups according to their chemical structuresČ steroidal and non-steroidal 17[beta]- hydroxysteroid dehydrogenase type 1 inhibitors. Their estrogenicž proliferative activities and selectivities over other 17[beta]-hydroxysteroid dehydrogenases that are involved in local regulation of estrogen action (types 2, 7 and 12) are also presented.
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