Computational Identification of Protein Tyrosine Phospatase-1B (PTP-1B) Inhibitors for Checking Type II Diabetes

Abstract

Protein tyrosine phosphatases (PTPs) are a family of enzyme that comprises of about 100 proteins which catalyze dephosphorylation of phosphotyrosine residues in protein substrates. Phosphotyrosine is a central element in cell signaling, and its activity is essential for cellular homeostasis and for appropriate responses to extracellular signals. PTP-1B antagonizes insulin signaling by reducing the activation state of the insulin receptor kinase, thereby inhibiting post-receptor signaling in insulin responsive tissue. The enzyme has generated a great deal of interest as a potential drug target, and PTP-1B null mice do not accumulate fat when placed on high-fat diet in contrast to their wild-type littermates. Unfortunately, due to the ~80% homology in the catalytic domain of the PTP super family, finding novel inhibitors that are specific for PTP-1B has so far been proven difficult. Furthermore, the progress towards developing an efficient PTP-1B antagonist for therapeutic use has also been hampered by low bioavailability of inhibitor tested in vivo. This led us to discover PTP-1B inhibitors computationally. We have screened a vast library of compounds. Virtual screening was performed and further molecular docking and ADMET studies have been done to find out best possible drug candidate.

Keywords: Phosphatases, enzyme, inhibitors, virtual screening, molecular docking

Cite this Article
Bharti DK, Chaudhary KK, Gupta SK et al. Computational identification of protein tyrosine phospatase-1B (PTP-1B) inhibitors for checking type II diabetes. Research & Reviews: Journal of Medical Science and Technology. 2017; 6(3): 21–25p.