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.

17β-Hydroxysteroid Dehydrogenase Type 1 Inhibition: A Potential Treatment Option for Non-Small Cell Lung Cancer

Abstract: In the face of the clinical challenge posed by non-small cell lung cancer (NSCLC), the present need for new therapeutic approaches is genuine. Up to now, no proof existed that 17β-hydroxysteroid de...

Insight into the Mechanism of 17β-Hydroxysteroid Dehydrogenase Type 3 Inhibition by the Androsterone Derivative RM-532-105

Abstract: The last step in the production of androgen testosterone from 4-androstene- 3,17-dione (4-dione) in testis involves the 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3). Blocking this microsomal enzyme with an inhibitor would lower the level of testosterone and, consequently, could be an approach for the treatment of androgen-dependent diseases. RM-532-105 was developed as a steroidal inhibitor of 17β-HSD3, but its mechanism of action is not yet known. To identify potential binding sites of the 17β-HSD3 substrate 4-dione, cofactor NADPH, as well as inhibitor RM-532-105. Since there is no crystal structure of 17β-HSD3 available, complexed or not with a ligand, a homology model was prepared followed by molecular docking, and enzymatic assay experiments were performed. Transfected LNCaP prostate cancer cells were used as a source of 17β-HSD3 activity for the transformation of 4-dione into testosterone in the presence of varying concentrations of a substrate, a cofactor or an inhibitor. Molecular modeling experiments and enzymatic assays with these cells suggest a competitive action of RM-532-105 with the cofactor and a non-competitive action with the substrate 4-dione. These results allow the selection of one inhibitor orientation in the enzyme binding site, from the two possibilities predicted by the docking experiments, and appear to be in agreement with previous structure-activity relationships.

Synthesis and Biological Evaluation of Phenyl Substituted 1H‐1,2,4‐Triazoles as Non‐Steroidal Inhibitors of 17β‐Hydroxysteroid Dehydrogenase Type 2.

Abstract: A series of disubstituted-1H-1,2,4-triazole derivatives was synthesized with the aim of developing new non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) - a novel and attractive target for the treatment of osteoporosis. 17βHSD2 catalyzes the oxidation of the highly active estrogen 17β-estradiol (E2) and androgen testosterone (T) into the weak estrone and androstenedione, respectively. Inhibition of this enzyme will locally in the bone lead to an increase in E2 and T levels, two key players in the maintenance of the balance between bone resorption and bone formation. In this study, a new class of 17βHSD2 inhibitors with a 1H-1,2,4-triazole scaffold was identified; the three best compounds 8b, 8f, and 13a showed moderate 17βHSD2 inhibitory activity and a good selectivity toward 17βHSD1. They could be a useful tool to map the unexplored enzyme active site.

Molecular Cloning and Characterization of the Human Gene for Interleukin-3 (IL-3)

Abstract: Interleukin 3 (IL-3) is a member of the family of colony stimulating factors (CSFs) responsible for regulating hematopoiesis (1). It is a T cell-derived lymphokine that was first defined by its ability to induce 20-α- hydroxysteroid dehydrogenase (20-α-SDH) in spleen cells of neonatal nude mice (2). IL-3 has been extensively characterized in the murine system. The protein was purified to homogeneity and both cDNA and genomic clones were subsequently isolated (3, 4, 5). With the availability of homogeneous protein, it has became apparent that this lymphokine is active in a variety of assays and is probably identical to a number of factors defined in other assay systems (6, 7). In vivo studies with recombinant murine IL-3 have indicated that IL-3 can stimulate erythropoiesis as well as myelopoiesis in both normal and myelo-suppressed mice (8, 9). Because of its broad spectrum of biological activities and its potential usage in treating bone marrow failure, there was considerable interest in isolating the human homologue of murine IL-3.