824983-91-7

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

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Tumey et al. (2005), The identification and optimization of a N-hydroxy urea series of flap endonuclease 1 inhibitors; Med. Chem. Lett., 15 277 Exell et al. (2016), Cellular Active N-Hydroxyurea FEN1 Inhibitors Block Substrate Entry to the Active Site; Chem. Biol., 12 815 Ward et al. (2017), Small molecules inhibitors uncover synthetic genetic interactions of human flap endonuclease 1 (FEN1) with DNA damage response genes; PLoS One, 12 e0179278 Guo et al. (2020), FEN1 endonuclease as a therapeutic target for human cancers with defects in homologous recombination; Natl. Acad. Sci USA 117 19415