Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.
Basic Information
ID: ALA1138469
Journal: J Med Chem
Title: Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.
Authors: Lehtiö L, Jemth AS, Collins R, Loseva O, Johansson A, Markova N, Hammarström M, Flores A, Holmberg-Schiavone L, Weigelt J, Helleday T, Schüler H, Karlberg T.
Abstract: Poly(ADP-ribose) polymerases (PARPs) activate DNA repair mechanisms upon stress- and cytotoxin-induced DNA damage, and inhibition of PARP activity is a lead in cancer drug therapy. We present a structural and functional analysis of the PARP domain of human PARP-3 in complex with several inhibitors. Of these, KU0058948 is the strongest inhibitor of PARP-3 activity. The presented crystal structures highlight key features for potent inhibitor binding and suggest routes for creating isoenzyme-specific PARP inhibitors.
CiteXplore: 19354255
DOI: 10.1021/jm900052j
Patent ID: ┄