Topic
Hydroxysteroid dehydrogenase
About: Hydroxysteroid dehydrogenase is a research topic. Over the lifetime, 1087 publications have been published within this topic receiving 28468 citations. The topic is also known as: hydroxysteroid dehydrogenase.
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TL;DR: It is found that treatment with T0901317, a nonspecific LXR agonist, increased both 17β-HSD13 mRNA and protein levels in cultured hepatocytes and demonstrates that LXRα activation induces 17 β- HSD13 expression in a SREBP-1c-dependent manner.
Abstract: Liver X receptors, including LXRα and LXRβ, are known to be master regulators of liver lipid metabolism. Activation of LXRα increases hepatic lipid storage in lipid droplets (LDs). 17β-Hydroxystero...
20 citations
TL;DR: Further structural variations on the bicyclic moiety are described, especially focusing on the exchange of its hydroxy function, and a molecular docking study provided insight into the protein–ligand interactions of this compound with 17β‐HSD1.
Abstract: An attractive target that has still to be explored for the treatment of estrogen-dependent diseases, such as breast cancer and endometriosis, is the enzyme responsible for the last step in the biosynthesis of estradiol (E2): 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1). It catalyzes the reduction of the weakly active estrone (E1) into E2, which is the most potent estrogen in humans. Inhibition of 17β-HSD1 lowers intracellular E2 concentrations and thus presents a therapeutic target for estrogen-dependent pathologies. Recently, we reported a new class of highly active and selective 17β-HSD1 inhibitors: bicyclic substituted hydroxyphenylmethanones. Here, further structural variations on the bicyclic moiety are described, especially focusing on the exchange of its hydroxy function. Twenty-nine novel inhibitors were synthesized and evaluated for 17β-HSD1 inhibition in a cell-free and cellular assay, for selectivity toward 17βHSD2 and estrogen receptors (ER) alpha and beta, as well as for metabolic stability. The best compound exhibited IC50 values of 12 nM (cell-free assay) and 78 nM (cellular assay), high selectivity for 17β-HSD1, and reasonable metabolic stability. A molecular docking study provided insight into the protein-ligand interactions of this compound with 17β-HSD1.
20 citations
TL;DR: 3β,17β‐Hydroxysteroid dehydrogenase (3β17/βHSDH) is an NAD‐dependent dehydrogen enzyme which has a double specificity for the 3‐ and 17‐positions on the steroid skeleton.
20 citations
TL;DR: Structures and kinetic properties of the wild-type and mutant enzymes indicate that Leu308 is a selectivity determinant for inhibitor binding, and 5-substituted 3-chlorosalicylic acid derivatives were synthesized, of which the most potent compound was 24-fold more selective for AKR1C1 relative to the structurally similar 3α-hydroxysteroid dehydrogenase.
20 citations
20 citations