The physiological effects of glucagon like peptide-1 (GLP-1) are of great interest because
of the potential clinical relevance of this peptide. In the pancreas, GLP-1 is believed to enhance insulin
secretion through mechanism involving the regulation of ion channels for manipulating in vivo
survival of GLP-1, two separate approaches can be seen-the development of analogs of GLP-1 or the
use of selective enzyme inhibitors DPP-IV inhibition is a viable approach to treating diabetes. We
have screened a vast library of compound and found ten best compounds with potent drug like activity
using virtual screening and docking methods. The best molecule was validated by molecular dynamic
simulation method. Type 2 diabetes mellitus is caused mainly due to an imbalance in the relationship
between glucagon like peptide-1 and insulin levels in plasma. Glucagon exerts its action
through activation of the glucagon receptor DPP-IV. These observations have prompted interest in
blockade of DPP-IV activity for the control of over production of hepatic glucose or the treatment of
type 2 diabetes mellitus. In the present study, a large virtual library of compounds was screened
against the crystal structure of DPP-IV to identify a favorable therapeutic choice of DPP-IV antagonist.
The interactions of lead compound with the ligand binding residues of DPP-IV were analyzed.
The proposed lead compound was also compared with some marketed preparation DPP-IV antagonists
for their binding affinity and other pharmacological properties. As a conclusion of this study,
we have identified a compound ZINC05998557 (6) as potent DPP-IV antagonist for the treatment of
type 2 diabetes mellitus.
Keywords: Diabetes, GLP-1, DPP-IV, Inhibitor, molecular docking, virtual screening, ADME/T, antagonist.
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