Sodium-glucose Cotransporter-2 Inhibitors as Modulator of Dipeptidyl Peptidase-4 in Diabetes

Indian Journal of Pharmaceutical Education and Research

  • Misbahuddin M. Rafeeq1Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah, SAUDI ARABIA.
  • Shahnaz Haque1Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah, SAUDI ARABIA.
  • Ziaullah M. Sain1Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah, SAUDI ARABIA.
  • Ahmad Alzamami2College of Applied Medical Science, Clinical Laboratory Science Department, Shaqra University, SAUDI ARABIA.
  • Norah A. Alturki3College of Applied Medical Science Clinical Laboratory Science Department King Saud University, Riyadh, SAUDI ARABIA.
  • Mutaib M. Mashraqi4Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, SAUDI ARABIA.
  • Youssef Saeed Alghamdi5Department of Biology, Turabah University College, Taif University, Taif, SAUDI ARABIA.
  • Rashed Ahmed Alniwaider6Department of Pathology and Laboratory Medicine, Ministry of National Guard Hospital and Health Affairs (MNGHA), SAUDI ARABIA.
  • Ayyub Patel7Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, SAUDI ARABIA.

Volume 55 Issue 4 Pages 1008-1016

DOI: 10.5530/ijper.55.4.201

Abstract

Background: Genetic disorders such as diabetes have severe implications on human health. Mutation or aberrant activity of different proteins are associated with diabetes. The hyperactivation of the peptidase function of dipeptidyl peptidase-4 (DPP4) strongly correlates with the elevated level of blood glucose in diabetic patients. Aim: Preventing the activity of DPP4 by small molecule modulators is an excellent approach that proposes to curb the aggressiveness of diabetes. Blocking the DPP4 function quantitatively raises glucagon-like peptide 1 (GLP-1) in the blood that finally lowers the level of glucose in circulating fluids. Materials and Methods: In this study, we have conducted an elaborate investigations of the sequence-based structural properties of DPP4 protein by using various computational methods in order to find protein’s antigenic and drug-binding regions. Results: Using the dataset of sodium-glucose transport protein 2 (SGLT2) inhibitors, we have identified a set of molecules that are predicted to bind DPP4. We have characterized the dipeptide ubenimex as the most potential modulator of DPP4. Conclusion: Based on the findings of current study, we concluded that our study has decoded the inhibitory module of DPP4 by the approach of structure-guided drug identification.

Keywords

  • SGLT2
  • DPP4
  • Docking
  • Diabetes
  • Ubenimex
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