Author/Authors :
Xiao-ling Cockcroft، نويسنده , , Krystyna J. Dillon، نويسنده , , Lesley Dixon، نويسنده , , Jan Drzewiecki، نويسنده , , Frank Kerrigan، نويسنده , , Vincent M. Loh Jr.، نويسنده , , Niall M.B. Martin، نويسنده , , Keith A. Menear، نويسنده , , Graeme C.M. Smith، نويسنده ,
Abstract :
We have previously described the discovery of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors based on a phthalazinone scaffold. Subsequent optimisation of inhibitory activity, metabolic stability and pharmacokinetic parameters has led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-one PARP-1 inhibitors which retain low nM cellular activity and show good stability in vivo and efficacy in cell based models.
Keywords :
PARP-1 inhibitor , Phthalazinone , DNA repair , Anti-cancer , BRCA2-deficient cell
