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Overview
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Background
Ki: 1 μM using 11-dehydrocorticosterone as substrateBVT 2733 is a novel, small molecule, non-steroidal, and selective inhibitor of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1).11β-HSD1 has been reported to alter glucocorticoid hormone action in target tissues for insulin action and is suggested to play a key role in glucose homeostasis.In vitro: BVT 2733 was identified as a novel type 1 selective inhibitor of murine 11β-HSD1 (Ki 1 μmol/l), which did not inhibit mouse 11β-HSD type 2 at a concentration as high as 200 μmol/l (corresponding to a Ki >33 μmol/l). Therefore, the selectivity of BVT 2733 for the 11β-HSD type 1 enzyme over the type 2 enzyme was estimated to be at least 30-fold based on the Ki values [1]. In vivo: In mice, BVT 2733 treatment could lower hepatic PEPCK and glucose-6-phosphatase mRNA, serum insulin and blood glucose concentrations compared with vehicle treated mice. In contrast, hepatic 11beta-hydroxysteroid dehydrogenase type 1 mRNA, liver function marker enzyme expression including alanine aminotransferase, aspartate aminotransferase and alkaline phosphatases, body weight as well as daily food intake were not changed by the treatment of BVT 2733 [1]. Clinical trial: Up to now, BVT 2733 is still in the preclinical development stage.
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