Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries

…, IR Hardcastle, C Richardson, L Rigoreau…

Index: Leahy, Justin J.J.; Golding, Bernard T.; Griffin, Roger J.; Hardcastle, Ian R.; Richardson, Caroline; Rigoreau, Laurent; Smith, Graeme C.M. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 24 p. 6083 - 6087

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Citation Number: 225

Abstract

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 ...