Recent Patents on Anti-Cancer Drug Discovery

Khurshid Zaman  
Bentham Science Publishers


Poly(ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors in Cancer Chemotherapy

Author(s): Victoria Cepeda, Miguel A. Fuertes, Josefina Castilla, Carlos Alonso, Celia Quevedo, Manual Soto and Jose M. Perez

Affiliation: Departmento de QuimicaInorganica, Facultad de Ciencias, Universidad Autonoma de Madrid, 28049-Madrid, Spain.

Keywords: PARP-1, inhibitors, cancer, chemotherapy


Poly(ADP-ribose) polymerases (PARPs) are defined as a family of cell signaling enzymes present in eukaryotes, which are involved in poly(ADP-ribosylation) of DNA-binding proteins. The best studied of these enzymes (PARP-1) is involved in the cellular response to DNA damage so that in the event of irreparable DNA damage overactivation of PARP-1 leads to necrotic cell death. Inhibitors of PARP-1 activity in combination with DNA-binding antitumor drugs may constitute a suitable strategy in cancer chemotherapy. When DNA is moderately damaged, PARP-1 participates in the DNA repair process and the cell survives. However, in the case of extensive DNA damage PARP-1 overactivation induces a decrease of NAD+ and ATP levels leading to cell dysfunction or even to necrotic cell death. So, due to PARP-1 involvement in cell death, pharmacological inhibition of PARP-1 activity by PARP-1 inhibitors may constitute a suitable target to enhance the activity of antitumor drugs through inhibition of necrosis and activation of apoptosis. PARP-1 inhibitors such as 3-aminobenzamide, 1,5-dihydroxyisoquinolinone and the recently patented tryciclic benzimidazoles have shown potent inhibitory effects of PARP-1 activity in tumor cells. The present review gives an update of the state-of-the-art of inhibition of PARP-1 activity as adjuvant therapy in cancer treatment.

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Article Details

Page: [39 - 53]
Pages: 15
DOI: 10.2174/157489206775246430