bms-309403 and Diabetes-Mellitus--Type-2

Present studies have shown that the lipid carrier has a significant role in several aspects of metabolic syndrome in A-FABP/ap2-deficient mice, including type 2 diabetes and atherosclerosis. 38 Thiazole- and indole-based derivatives were synthesized and investigated for their inhibitory effects on the production of LPS-stimulated TNF-α. Among them, 12b exhibited an excellent inhibitory efficiency compared to BMS309403 (95% vs. 85%) at the concentration of 10 μM and a binding affinity for ap2 with the apparent K(i) values 33 nM. Oral administration of 12b at a dosage of 50 mg/kg effectively reduced the levels of plasma blood glucose, triglycerides, insulin, total cholesterol and alanine aminotransferase in high-fat/diet-induced obesity model. The results highlighted that 12b was a potent anti-diabetic agent.

Topics: Administration, Oral; Alanine Transaminase; Animals; Blood Glucose; Body Weight; Cell Line; Cholesterol; Diabetes Mellitus, Type 2; Drug Design; Fatty Acid-Binding Proteins; Hypoglycemic Agents; Indoles; Insulin; Lipopolysaccharides; Male; Mice; Models, Molecular; Protein Conformation; Rats; Structure-Activity Relationship; Thiazoles; Triglycerides; Tumor Necrosis Factor-alpha