High-throughput identification of inhibitors of human mitochondrial peptide deformylase Academic Article uri icon


MeSH Major

  • Amidohydrolases
  • Enzyme Inhibitors
  • Mitochondria


  • The human mitochondrial peptide deformylase (HsPDF) provides a potential new target for broadly acting antiproliferative agents. To identify novel nonpeptidomimetic and nonhydroxamic acid-based inhibitors of HsPDF, the authors have developed a high-throughput screening (HTS) strategy using a fluorescence polarization (FP)-based binding assay as the primary assay for screening chemical libraries, followed by an enzymatic-based assay to confirm hits, prior to characterization of their antiproliferative activity against established tumor cell lines. The authors present the results and performance of the established strategy tested in a pilot screen of 2880 compounds and the identification of the 1st inhibitors. Two common scaffolds were identified within the hits. Furthermore, cytotoxicity studies revealed that most of the confirmed hits have antiproliferative activity. These findings demonstrate that the designed strategy can identify novel functional inhibitors and provide a powerful alternative to the use of functional assays in HTS and support the hypothesis that HsPDF inhibitors may constitute a new class of antiproliferative agent.

publication date

  • June 2007



  • Academic Article



  • eng

PubMed Central ID

  • PMC2234356

Digital Object Identifier (DOI)

  • 10.1177/1087057107300463

PubMed ID

  • 17435169

Additional Document Info

start page

  • 521

end page

  • 35


  • 12


  • 4