Enzyme Engineering
Open Access

Abstract

In Silico Identification of Novel Glucagon Receptor Antagonist for the Treatment of Type 2 Diabetes Mellitus

Utkarsh Raj, Yashasvi Jain, Himansu Kumar, Saurabh Gupta, Rashmi Tripathi and Pritish Kumar Varadwaj

Type 2 diabetes mellitus is caused mainly due to an imbalance in the relationship between glucagon and insulin levels in plasma. To counteract the actions of insulin and maintain normoglycemia during the fasting state by inducing hepatic glucose production are the major biological action of glucagon. Glucagon exerts its action through activation of the glucagon receptor (GCGR). These observations have prompted interest in blockade of GCGR 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 GCGR to identify a favorable therapeutic choice of GCGR antagonist. The interactions of lead compound with the active site of GCGR were analyzed and molecular dynamics study was also performed to check its stability in the receptor pocket. The proposed lead compound was also compared with some already reported GCGR antagonists for their binding affinity and other pharmacological properties. As a conclusion of this study, we have identified a compound STOCK1N82694 as potent GCGR antagonist for the treatment of type 2 diabetes mellitus.