title: An Integrated Computational Approach for Plant-Based Protein Tyrosine Phosphatase Non-Receptor Type 1 Inhibitors.
abstract: BACKGROUND
  Protein tyrosine phosphatase non-receptor type 1 is a therapeutic target for the type 2 diabetes mellitus. According to the International Diabetes Federation 2015 report, one out of 11 adults suffers from diabetes mellitus globally.
  
  
  OBJECTIVE
  Current anti-diabetic drugs can cause life-threatening side-effects. The present study proposes a pipeline for the development of effective and plant-derived anti-diabetic drugs that may be safer and better tolerated.
  
  
  METHODS
  Plant-derived protein tyrosine phosphatase non-receptor type 1 inhibitors possessing antidiabetic activity less than 10µM were used as a training set. A common feature pharmacophore model was generated. Pharmacophore-based screening of plant-derived compounds of the ZINC database was conducted using ZINCpharmer. Screened hits were assessed to evaluate their drug-likeness, pharmacokinetics, detailed binding behavior, and aggregator possibility based on their physiochemical properties and chemical similarity with reported aggregators.
  
  
  RESULTS
  Through virtual screening and in silico pharmacology protocol isosilybin (ZINC30731533) was identified as a lead compound with optimal properties. This compound can be recommended for laboratory tests and further analyses to confirm its activity as protein tyrosine phosphatase nonreceptor type 1 inhibitor.
  
  
  CONCLUSIONS
  The present study has identified plant-derived anti-diabetic virtual lead compound with the potential to inhibit protein tyrosine phosphatase non-receptor type 1, which may be helpful to enhance insulin production. This computer-aided study could facilitate the development of novel pharmacological inhibitors for diabetes treatment.
authors.affiliation: Department of Environment and Life Engineering, Graduate School of Engineering, Maebashi Institute of Technology, Maebashi, Japan.
authors.forename: Shabana
authors.initials: S
authors.lastname: Bibi
authors.affiliation: Department of Environment and Life Engineering, Graduate School of Engineering, Maebashi Institute of Technology, Maebashi, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Sakata
mesh_terms: D017076:Computer-Aided Design; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology; D062105:Molecular Docking Simulation; D010944:Plants / Q000737:chemistry*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D012838:Silymarin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D012838:Silymarin; C075820:isosilybin; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Computer-aided drug design; common feature pharmacophore modeling; diabetes mellitus; flavonoids; isosilybin; molecular docking; pharmacokinetics.; protein tyrosine phosphatase non-receptor
  type 1