Due to its crucial role in nucleotide metabolism, adenylate kinase deserves a special attention in screening of potential inhibitors. Herein, we report the assessment of the relative orientation of the ligand 2,4thiazolidinedione to adenylate kinase crystallized in closed conformation. Protein-ligand docking was performed to estimate the binding energy and inhibition constant of 2,4-thiazolidin...

OBJECTIVE To compare the effects of monotherapy using nateglinide and the thiazolidinedione troglitazone with initial combination of the two agents on glycated hemoglobin (HbA(1c)) in patients with type 2 diabetes inadequately controlled by diet alone. RESEARCH DESIGN AND METHODS This study consisted of a 28-week, double-blind, randomized, multicenter study that included a 4-week, single-blin...

Saxagliptin (Onglyza™) is a potent, selective, once-daily dipeptidyl peptidase-4 (DPP-4) inhibitor indicated for improving glycemic control in patients with type 2 diabetes (T2D). By blocking DPP-4, saxagliptin increases and prolongs the effects of incretins, a group of peptide hormones released by intestinal cells after meals, which stimulate glucose-dependent insulin secretion to lower blood ...

Increased accumulation of fatty acids and their derivatives can impair insulin-stimulated glucose disposal by skeletal muscle. To characterize the nature of the defects in lipid metabolism and to evaluate the effects of thiazolidinedione treatment, we analyzed the levels of triacylglycerol, long-chain fatty acyl-coA, malonyl-CoA, fatty acid oxidation, AMP-activated protein kinase (AMPK), acetyl...

The first dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin was approved in 2006 as treatment for diabetes concurrently with lifestyle changes. A combined product of sitagliptin and glucophage was approved by the U.S. Food and Drug Administration in 2007. The second DPP-4 inhibitor, saxagliptin, was approved in theU.S. It was approved both as monotherapy as well as in combination with metform...

Thiazolidinediones (TZDs) have been found to act as effective quorum sensing quenchers, capable of preventing biofilm formation. Our previous studies demonstrated a profound antibiofilm effect of the TZD derivative thiazolidinedione-8 (S-8), either in solution or incorporated into a sustained-release membrane (SRM-S-8) under batch conditions. In the present study, we used a constant depth film ...

A series of synthesized and commercially available compounds were assessed against PI3Kα for in vitro inhibitory activity and the results compared to binding calculated in silico. Using published crystal structures of PI3Kγ and PI3Kδ co-crystallized with inhibitors as a template, docking was able to identify the majority of potent inhibitors from a decoy set of 1000 compounds. On the other hand...

BACKGROUND Synthesized arylidene derivatives of rhodanine and 2,4-thiazolidiendione have potent pharmacological activities, and these are also key substrates for the preparation of clinically used antidiabetics. FINDINGS Some 1,1,3,3-tetramethylguanidine-based task-specific ionic liquids (TSILs) 1a-1e were prepared and employed to the catalyzed solvent-free Knoevenagel condensation of 2,4-thi...