De novo design based pharmacophore query generation and virtual screening for the discovery of Hsp-47 inhibitors

Biochem Biophys Res Commun. 2015 Jan 16;456(3):707-13. doi: 10.1016/j.bbrc.2014.12.051. Epub 2014 Dec 16.

Abstract

Heat shock protein-47 (Hsp-47) is exclusive collagen specific molecular chaperone involved in the maturation, processing and secretion of procollagen. Hsp-47 is consistently upregulated in several fibrotic diseases. Till date there is no potential antifibrotic small molecule drug available and Hsp-47 is known to be potential therapeutic target for fibrotic disorder and drug designing. We used the de novo drug design approach followed by pharmacophore generation and virtual screening to propose Hsp-47 based antifibrotic molecules. We used e-LEAD server for de novo drug design and ZINCPharmer for 3D pharmacophore generation and virtual screening. The virtually screened molecule may inhibit direct recruitment of collagen triple helix to interact with Hsp-47 and act as antifibrotic drug.

Keywords: De novo drug designing; Heat shock protein 47; Pharmacophore; Virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Collagen / chemistry*
  • Computer Simulation
  • Crystallography, X-Ray
  • Drug Design*
  • Drug Evaluation, Preclinical / methods
  • Fibrosis / drug therapy
  • HSP47 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP47 Heat-Shock Proteins / chemistry*
  • Humans
  • Imaging, Three-Dimensional / methods*
  • Models, Chemical
  • Software

Substances

  • HSP47 Heat-Shock Proteins
  • Collagen