PARP Inhibitor Development for Systemic Cancer Targeting

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 17, 14 Issues, 2017

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

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PARP Inhibitor Development for Systemic Cancer Targeting

Anti-Cancer Agents in Medicinal Chemistry, 7(5): 515-523.

Author(s): Tomasz Zaremba and Nicola Jane Curtin.

Affiliation: Newcastle University,Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.


Poly(ADP-ribose) polymerase 1 (PARP-1) is a DNA-binding enzyme that is activated by DNA breaks, converting them into an intracellular signal via poly(ADP-ribosyl)ation of nuclear proteins. Negatively charged polymers of ADP-ribose (PAR) attached to PARP-1 itself and histones lead to chromatin relaxation, facilitating the access of base excision/single strand break repair proteins and activating these repair enzymes. PARP inhibitors have been developed to investigate the role of PARP-1 in cell biology and to overcome DNA repair-mediated resistance of cancer cells to cytotoxic therapy. Since the early benzamide inhibitors of the 1980s PARP inhibitors, developed through structure-activity relationships and crystal structure-based drug design, that are 1,000x more potent have been identified. These novel PARP inhibitors have been shown to enhance the antitumour activity of temozolomide (a DNA-methylating agent), topoisomerase poisons and ionising radiation in advanced pre-clinical studies and are now under clinical evaluation. PARP inhibitors can also selectively kill cells and tumours with homozygous defects in the hereditary breast cancer genes, BRCA1 and BRCA2.


Base excision repair/single strand break repair, Poly(ADP-ribose) polymerase-1 (PARP-1), PARP inhibitors.

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Article Details

Volume: 7
Issue Number: 5
First Page: 515
Last Page: 523
Page Count: 9
DOI: 10.2174/187152007781668715
Price: $58

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