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

• Published in: Biochemical and biophysical research communications 2015-01, Vol.456 (3), p.707-713
• Main Authors: Katarkar, Atul, Haldar, Pallab Kanti, Chaudhuri, Keya
• Format: Article
• Language: English
• Subjects: Binding Sites; Collagen - chemistry; Computer Simulation; Crystallography, X-Ray; De novo drug designing; Drug Design; Drug Evaluation, Preclinical - methods; Fibrosis - drug therapy; Heat shock protein 47; HSP47 Heat-Shock Proteins - antagonists & inhibitors; HSP47 Heat-Shock Proteins - chemistry; Humans; Imaging, Three-Dimensional - methods; Models, Chemical; Pharmacophore; Software; Virtual screening
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.12.051

•Implementation of e-LEA3D server for de novo based Hsp-47 inhibitors designing.•Retrieval of 15 potential lead optimized Hsp-47 inhibitors.•ZINC15085064 and ZINC65001938 may serve as potential Hsp-47 inhibitor. 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.