title: De novo design based pharmacophore query generation and virtual screening for the discovery of Hsp-47 inhibitors.
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.
authors.affiliation: Molecular & Human Genetics Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Katarkar
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
authors.forename: Pallab Kanti
authors.initials: PK
authors.lastname: Haldar
authors.affiliation: Molecular & Human Genetics Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032, India. Electronic address: kchaudhuri@iicb.res.in.
authors.forename: Keya
authors.initials: K
authors.lastname: Chaudhuri
mesh_terms: D001665:Binding Sites; D003094:Collagen / Q000737:chemistry*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005355:Fibrosis / Q000188:drug therapy; D050958:HSP47 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008956:Models, Chemical; D012984:Software
chemical_list: D050958:HSP47 Heat-Shock Proteins; D003094:Collagen
keywords: De novo drug designing; Heat shock protein 47; Pharmacophore; Virtual screening