Structure-based design of HSPA5 inhibitors: From peptide to small molecule inhibitors

Meilan Huang*, Zhuo Li, Dawei Li, Steven Walker, Caroline Greenan, Richard Kennedy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

We identified nine small-molecule hit compounds of Heat shock 70 kDa 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. 

Original languageEnglish
Pages (from-to)3044-3050
JournalBioorganic & Medicinal Chemistry Letters
Volume23
Issue number10
Early online date16 Mar 2013
DOIs
Publication statusPublished - 15 May 2013

Keywords

  • Peptide substrate
  • Apoptosis
  • HEAT-SHOCK-PROTEIN
  • HSP70
  • HSP90
  • CHAPERONE DNAK
  • Cancer
  • In silico screening
  • INDUCED APOPTOSIS
  • SUBSTRATE-BINDING
  • IDENTIFICATION
  • HSP70 inhibitors
  • HEAT-SHOCK-PROTEIN-70
  • SPECIFICITY
  • MODULATORS

Cite this