Tu, Hua published the artcileDistinctive molecular inhibition mechanisms for selective inhibitors of human 11β-hydroxysteroid dehydrogenase type 1, Quality Control of 97009-67-1, the main research area is sulfonamide triazole hydroxysteroid dehydrogenase inhibitor preparation; non insulin dependent diabetes antidiabetic hydroxysteroid dehydrogenase inhibitor.
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the NADPH dependent interconversion of inactive cortisone to active cortisol. Excess 11β-HSD1 or cortisol leads to insulin resistance and metabolic syndrome in animal models and in humans. Inhibiting 11β-HSD1 activity signifies a promising therapeutic strategy in the treatment of Type 2 diabetes and related diseases. Herein, the authors report two highly potent and selective small mol. inhibitors of human 11β-HSD1. While compound (I), a sulfonamide, functions as a simple substrate competitive inhibitor, compound (II), a triazole, shows the kinetic profile of a mixed inhibitor. Co-crystal structures reveal that both compounds occupy the 11β-HSD1 catalytic site, but present distinct mol. interactions with the protein. Strikingly, compound (II) interacts much closer to the cofactor NADP+ and likely modifies its binding. Together, the structural and kinetic analyses demonstrate two distinctive mol. inhibition mechanisms, providing valuable information for future inhibitor design.
Bioorganic & Medicinal Chemistry published new progress about Antidiabetic agents. 97009-67-1 belongs to class nitriles-buliding-blocks, name is 1-(4-Fluorophenyl)cyclopropanecarbonitrile, and the molecular formula is C10H8FN, Quality Control of 97009-67-1.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts