BVT-2733

A non-steroidal, isoform-selective inhibitor of mouse 11β-HSD1 with Ki of 1 uM; displays >20-fold selectivity over 11β-HSD2; lowers hepatic PEPCK and glucose-6-phosphatase mRNA, blood glucose and serum insulin concentrations in a hyperglycaemic and hyperinsulinaemic mouse model.Diabetes Preclinical(In Vitro):BVT 2733 (100 μM; 24 hours) co-treatment with PA (100 μM) reduces MCP-1 expression in fully differentiation adipocytes.BVT 2733 (50-100 μM; 24 hours) reduces the inflammation protein levels (MCP-1, IL-6) in medium in J774.1 macrophages by Elisa.(In Vivo):BVT-2733 (oral administration; 100 mg/kg; twice daily; 2 weeks) attenuates the arthritis severity and anti-CII level and decreases the levels of serum TNF-α, IL-1β, IL-6 and IL-17 in CIA mice.BVT 2733 (oral administration; 100 mg/kg; dosed (09.00 and 17.00 h); last 4 weeks) exhibits decreased body weight and enhanced glucose tolerance and insulin sensitivity when it compares to control mice. It also down-regulated the expression of inflammation-related genes including monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α) and the number of infiltrated macrophages within the adipose tissue in vivo.