Computational Identification of Inhibitors Against DPP-IV for Checking Type-2 Diabetes

Author(s): Sarvesh Kumar Gupta, Kamal Kumar Chaudhary, Utkarsh Raj, Nidhi Mishra.

Journal Name: Letters in Drug Design & Discovery

Volume 14 , Issue 1 , 2017

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Abstract:

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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Article Details

VOLUME: 14
ISSUE: 1
Year: 2017
Page: [66 - 73]
Pages: 8
DOI: 10.2174/1570180813666160720121718
Price: $58

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