PARP inhibition: PARP1 and beyond.
Recent findings have thrust poly(ADP-ribose) polymerases (PARPs) into the limelight as potential chemotherapeutic targets. To provide a framework for understanding these recent observations, we review what is known about the structures and functions of the family of PARP enzymes, and then outline a series of questions that should be addressed to guide the rational development of PARP inhibitors as anticancer agents.
Rouleau
Michèle
M
Laval University Medical Research Center, Laval University, Québec, Canada.
Patel
Anand
A
Hendzel
Michael J
MJ
Kaufmann
Scott H
SH
Poirier
Guy G
GG
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016923:Cell Death; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D051379:Mice; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D013379:Substrate Specificity; D000077204:Temozolomide; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D003841:Deoxycytidine; D003606:Dacarbazine; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D000077204:Temozolomide; D000093542:Gemcitabine