Description
LNT 1 (824983-91-7) is a potent (IC50 = 11 nM) inhibitor of flap endonuclease 1 (FEN1).1 It showed similar potency in inhibiting exonuclease 1 (EXO1).2 Induces a DNA damage response and ultimately cell death. FEN1 inhibitors have therapeutic potential for the treatment of cancers that are defective for homologous repair and other DNA repair and DNA damage checkpoint pathways.4
References
[1] L. NATHAN TUMEY. The identification and optimization of a N-hydroxy urea series of flap endonuclease 1 inhibitors[J]. Bioorganic & Medicinal Chemistry Letters, 2005, 15 2: Pages 277-281. DOI:
10.1016/j.bmcl.2004.10.086[2] JACK C EXELL. Cellularly active N-hydroxyurea FEN1 inhibitors block substrate entry to the active site[J]. Nature chemical biology, 2016, 12 10: 815-821. DOI:
10.1038/nchembio.2148[3] THOMAS A WARD Stephen T D Peter J McHugh. Small molecule inhibitors uncover synthetic genetic interactions of human flap endonuclease 1 (FEN1) with DNA damage response genes.[J]. PLoS ONE, 2017: e0179278. DOI:
10.1371/journal.pone.0179278[4] ELAINE GUO. FEN1 endonuclease as a therapeutic target for human cancers with defects in homologous recombination.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2020: 19415-19424. DOI:
10.1073/pnas.2009237117
