3.1.3.32 2-(1-hydroxyundecyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione A12B4C3 5856 3.1.3.32 2-(1-hydroxyundecyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione i.e. A12B4C3, a potent, noncompetitive inhibitor of the phosphatase activity of human polynucleotide kinase/phosphatase in vitro. The inhibitor can form a ternary complex with PNKP and a DNA substrate, the inhibitor does not prevent DNA from binding to the phosphatase DNA binding site, but disrupts the secondary structure of PNKP, interaction between Trp402 of PNKP and the inhibitor. A12B4C3 sensitizes A549 human lung cancer cells to the topoisomerase I poison, camptothecin, but not the topoisomerase II poison, etoposide, in a manner similar to small interferingRNAagainst PNKP 5856 3.1.3.32 2-(hydroxy(3,4,5-trimethoxyphenyl)methyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione A6B4C3 39792 3.1.3.32 2-(hydroxy(phenyl)methyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione A1B4C3 77449 3.1.3.32 2-(hydroxy(thiophen-2-yl)methyl)-6-methyl-1-(phenylamino)-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione A39B1C2 77450 3.1.3.32 diphosphate no effect on 3'-phosphatase, inhibition of 5'-hydroxyl kinase 17 3.1.3.32 EDTA - 21 3.1.3.32 heparin - 227 3.1.3.32 heparin heparin exhibits an IC50 of 0.16 mg/ml 227 3.1.3.32 additional information optimization of a rapid high-throughput screening method for detection of DNA 3'-phosphatases and their inhibitors, overview 2 3.1.3.32 additional information sensitivity to methyl methanesulfonate of all single and double mutant combinations of nth1, apn2, tdp1 and pnk1 2 3.1.3.32 NaCl can replace Mg2+ at 50 mM, inhibitory at 250 mM 42 3.1.3.32 NaCl best stimulation at 100 mM, inhibitory above 200 mM 42 3.1.3.32 PO43- 5'-hydroxyl kinase, little effect on 3'-phosphatase 867 3.1.3.32 SO42- 5'-hydroxyl kinase, little effect on 3'-phosphatase 245 3.1.3.32 tert-butyl 2-(1-hydroxy-2,2-diphenylethyl)-6-methyl-5,7-dioxo-2,4a,5,6,7,7a-hexahydro-1H-pyrrolo[3,4-b]pyridin-1-ylcarbamate A26B11C2 155609