Poly(ADP-ribose) polymerase inhibition in cancer therapy: are we close to maturity?
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.
Papeo
Gianluca
G
Department of Medicinal Chemistry, Nerviano Medical Sciences, Viale Pasteur 10, Nerviano (MI), Italy.
Forte
Barbara
B
Orsini
Paolo
P
Perrera
Claudia
C
Posteri
Helena
H
Scolaro
Alessandra
A
Montagnoli
Alessia
A
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
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases