Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries
JJJ Leahy, BT Golding, RJ Griffin, IR Hardcastle… - Bioorganic & medicinal …, 2004 - Elsevier
JJJ Leahy, BT Golding, RJ Griffin, IR Hardcastle, C Richardson, L Rigoreau, GCM Smith
Bioorganic & medicinal chemistry letters, 2004•ElsevierA solution-phase multiple-parallel synthesis approach was employed for the preparation of 6-
, 7-and 8-aryl-substituted chromenone libraries, which were screened as inhibitors of the
DNA repair enzyme DNA-dependent protein kinase (DNA-PK). These studies resulted in the
identification of 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441) as a
highly potent and selective DNA-PK inhibitor (IC50= 14nM), exhibiting ATP-competitive
inhibition kinetics.
, 7-and 8-aryl-substituted chromenone libraries, which were screened as inhibitors of the
DNA repair enzyme DNA-dependent protein kinase (DNA-PK). These studies resulted in the
identification of 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441) as a
highly potent and selective DNA-PK inhibitor (IC50= 14nM), exhibiting ATP-competitive
inhibition kinetics.
A solution-phase multiple-parallel synthesis approach was employed for the preparation of 6-, 7- and 8-aryl-substituted chromenone libraries, which were screened as inhibitors of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). These studies resulted in the identification of 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441) as a highly potent and selective DNA-PK inhibitor (IC50=14nM), exhibiting ATP-competitive inhibition kinetics.
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