Abstract
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.
Keywords: PARP-1, inhibitors, cancer, chemotherapy
Recent Patents on Anti-Cancer Drug Discovery
Title: Poly(ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors in Cancer Chemotherapy
Volume: 1 Issue: 1
Author(s): Victoria Cepeda, Miguel A. Fuertes, Josefina Castilla, Carlos Alonso, Celia Quevedo, Manual Soto and Jose M. Perez
Affiliation:
Keywords: PARP-1, inhibitors, cancer, chemotherapy
Abstract: 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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Cepeda Victoria, Fuertes A. Miguel, Castilla Josefina, Alonso Carlos, Quevedo Celia, Soto Manual and Perez M. Jose, Poly(ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors in Cancer Chemotherapy, Recent Patents on Anti-Cancer Drug Discovery 2006; 1 (1) . https://dx.doi.org/10.2174/157489206775246430
DOI https://dx.doi.org/10.2174/157489206775246430 |
Print ISSN 1574-8928 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3970 |
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