Take Y, Kumano M, Hamano Y, Fukatsu H, Teraoka H, Nishimura S, Okuyama A
Banyu Tsukuba Research Institute, Merck Research Laboratories, Tsukuba, Japan.
Biochem Biophys Res Commun. 1995 Oct 4;215(1):41-7. doi: 10.1006/bbrc.1995.2431.
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 microM, 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.
