Finding new scaffolds of JAK3 inhibitors in public database: 3D-QSAR models & shape-based screening

Arch Pharm Res. 2015 Nov;38(11):2008-19. doi: 10.1007/s12272-015-0607-6. Epub 2015 May 9.

Abstract

The STAT/JAK3 pathway is a well-known therapeutic target in various diseases (ex. rheumatoid arthritis and psoriasis). The therapeutic advantage of JAK3 inhibition motivated to find new scaffolds with desired DMPK. For the purpose, in silico high-throughput sieves method is developed consisting of a receptor-guided three-dimensional quantitative structure-activity relationship study and shape-based virtual screening. We developed robust and predictive comparative molecular field analysis (q (2) = 0.760, r (2) = 0.915) and comparative molecular similarity index analysis (q (2) = 0.817, r (2) = 0.981) models and validated these using a test set, which produced satisfactory predictions of 0.925 and 0.838, respectively.

Keywords: 3D-QSAR; Anti-inflammatory; Diversity of scaffolds; JAK3 inhibitors; Shape-based screening.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Computer Simulation
  • Drug Design*
  • Enzyme Inhibitors / pharmacology*
  • High-Throughput Screening Assays
  • Humans
  • Janus Kinase 3 / antagonists & inhibitors*
  • Models, Molecular*
  • Quantitative Structure-Activity Relationship
  • STAT Transcription Factors / metabolism

Substances

  • Enzyme Inhibitors
  • STAT Transcription Factors
  • JAK3 protein, human
  • Janus Kinase 3