title: Poly(ADP-ribose) polymerase inhibition in cancer therapy: are we close to maturity?
abstract: BACKGROUND
  During the last few years an increasing number of poly(ADP-ribose) polymerase (PARP) inhibitors have been appearing in the context of cancer therapy. This is mainly due to a better knowledge of the best-characterized member of the PARP family of enzymes, PARP-1, further reinforced by the recognition of the clinical benefits arising from its inhibition.
  
  
  OBJECTIVE
  The aim of this review is to give the reader an update on PARP inhibition in cancer therapy, by covering both the scientific (SciFinder) search) and the patent literature (Chemical Abstract/Derwent search) published recently (2005-2008).
  
  
  CONCLUSIONS
  More patient-compliant orally available PARP-1 inhibitor clinical candidates, along with their possible use as single agents in specific, molecularly defined cancer indications, increase the expectations for this therapeutic approach. The growing understanding of the biological role of other PARPs, such as Tankyrase 1, may be of interest as new potential targets. Besides the classical NAD-mimicking pharmacophore, additional compounds, which either do not resemble nicotinamide or exploit different binding sites, are emerging.
authors.affiliation: Department of Medicinal Chemistry, Nerviano Medical Sciences, Viale Pasteur 10, Nerviano (MI), Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Papeo
authors.forename: Barbara
authors.initials: B
authors.lastname: Forte
authors.forename: Paolo
authors.initials: P
authors.lastname: Orsini
authors.forename: Claudia
authors.initials: C
authors.lastname: Perrera
authors.forename: Helena
authors.initials: H
authors.lastname: Posteri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Scolaro
authors.forename: Alessia
authors.initials: A
authors.lastname: Montagnoli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D010330:Patents as Topic; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases