title: Structure-based design of HSPA5 inhibitors: from peptide to small molecule inhibitors.
abstract: We identified nine small-molecule hit compounds of Heat shock 70kDa protein 5 (HSPA5) from cascade in silico screening based on the binding modes of the tetrapeptides derived from the peptide substrate or inhibitors of Escherichia coli HSP70. Two compounds exhibit promising inhibition activities from cancer cell viability and tumor inhibition assays. The binding modes of the hit compounds provide a platform for development of selective small molecule inhibitors of HSPA5.
authors.affiliation: School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, UK. m.huang@qub.ac.uk
authors.forename: Meilan
authors.initials: M
authors.lastname: Huang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.forename: Steven
authors.initials: S
authors.lastname: Walker
authors.forename: Caroline
authors.initials: C
authors.lastname: Greenan
authors.forename: Richard
authors.initials: R
authors.lastname: Kennedy
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D045325:HCT116 Cells; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D010455:Peptides; D054852:Small Molecule Libraries