BVT 2733

Ki: 1 μM using 11-dehydrocorticosterone as substrate

BVT 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.

Reference:
[1] Alberts P,Engblom L,Edling N,Forsgren M,Klingstrm G,Larsson C,Rnquist-Nii Y,Ohman B,Abrahmsén L.  Selective inhibition of 11beta-hydroxysteroid dehydrogenase type 1 decreases blood glucose concentrations in hyperglycaemic mice. Diabetologia.2002 Nov;45(11):1528-32.