OK-1035, a Selective Inhibitor of DNA-Dependent Protein Kinase

OK-1035, a Selective Inhibitor of DNA-Dependent Protein Kinase

Screening for inhibitors of DNA-dependent protein kinase (DNA-PK) revealed 3-cyano-5-(4-pyridyl)-6-hydrazonomethyl-2-pyridone, designated OK-1035, to be a potent and selective inhibitor. When a synthetic peptide was used as a substrate, OK-1035 caused 50% inhibition of DNA-PK activity at 8 μM, a con...

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Veröffentlicht in:Biochemical and biophysical research communications 1995-10, Vol.215 (1), p.41-47
Hauptverfasser: Take, Y., Kumano, M., Hamano, Y., Fukatsu, H., Teraoka, H., Nishimura, S., Okuyama, A.
Format: Artikel
Sprache:eng
Schlagworte:
Amino Acid Sequence
Caseins - metabolism
Consensus Sequence
DNA-Activated Protein Kinase
DNA-Binding Proteins
Enzyme Inhibitors - pharmacology
HeLa Cells - enzymology
Humans
Hydrazones - chemistry
Hydrazones - pharmacology
Kinetics
Molecular Sequence Data
Molecular Structure
Nuclear Proteins
Peptides - chemistry
Peptides - metabolism
Phosphorylation
Phosphoserine - metabolism
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - metabolism
Pyridones - chemistry
Pyridones - pharmacology
Structure-Activity Relationship
Tumor Suppressor Protein p53 - metabolism
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Zusammenfassung:Screening for inhibitors of DNA-dependent protein kinase (DNA-PK) revealed 3-cyano-5-(4-pyridyl)-6-hydrazonomethyl-2-pyridone, designated OK-1035, to be a potent and selective inhibitor. When a synthetic peptide was used as a substrate, OK-1035 caused 50% inhibition of DNA-PK activity at 8 μM, a concentration more than 50 times lower than those required against seven other protein kinases tested. OK-1035 inhibited the phosphorylation by DNA-PK of consensus peptide as well as that of recombinant human wild type-p53. Kinetic studies indicated that OK-1035 inhibited DNA-PK activity in an ATP-competitive manner.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1995.2431