The identification and optimization of 2,4-diketobutyric acids as flap endonuclease 1 inhibitors

Bioorg Med Chem Lett. 2004 Oct 4;14(19):4915-8. doi: 10.1016/j.bmcl.2004.07.028.


There have been several recent reports of chemopotentiation via inhibition of DNA repair processes. Flap endonuclease 1 (FEN1) is a key enzyme involved in base excision repair (BER), a primary pathway utilized by mammalian cells to repair DNA damage. In this report, we describe the identification and SAR of a series of 2,4-diketobutyric acid FEN1 inhibitors.

MeSH terms

  • Butyrates / chemical synthesis*
  • Butyrates / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Flap Endonucleases / antagonists & inhibitors*
  • Structure-Activity Relationship


  • Butyrates
  • Enzyme Inhibitors
  • Flap Endonucleases