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2005
Enzyme inhibiting activity
X 0220
Identification of a Highly Potent and Selective DNA-Dependent Protein Kinase
Inhibitor (NU7441) by Screening of Chromenone Libraries. — The
15- 243 (DNA-PK)
use of a solution-phase multi-parallel synthesis yields 6-, 7-, and 8-aryl-substituted
chromenone libraries. Screening of focused libraries leads to the identification of structurally similar chromenones (I) as highly potent inhibitors of the DNA repair
enzyme DNA-dependent protein kinase. ATP-competitive inhibition kinetics are
established for the more potent dibenzothiophenyl derivative (Ib). This compound
retains excellent selectivity for DNA-PK over other PIKK family members. —
(LEAHY, J. J. J.; GOLDING, B. T.; GRIFFIN*, R. J.; HARDCASTLE, I. R.;
RICHARDSON, C.; RIGOREAU, L.; SMITH, G. C. M.; Bioorg. Med. Chem. Lett. 14
(2004) 24, 6083-6087; Inst. Cancer Res., Sch. Nat. Sci., Univ. Newcastle,
Newcastle upon Tyne NE1 7RU, UK; Eng.) — H. Hoennerscheid
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