PURPOSE Poly(ADP-ribose) polymerase (PARP) inhibitors selectively target homologous recombination (HR)-defective cells and show good clinical activity in hereditary breast and ovarian cancer associated with BRCA1 or BRCA2 mutations. A high proportion (up to 50%) of sporadic epithelial ovarian cancers (EOC) could be deficient in HR due to genetic or epigenetic inactivation of BRCA1/BRCA2 or othe...

To many investigators PARP1 is simply a substrate for caspase 3, and whose cleavage is thought indicative of apoptosis. However, in reality PARP1 plays a major role in the biology of the cell cycle and DNA repair. (1)(,) (2) PARP1 binds to damaged DNA where it becomes enzymatically activated and ADP ribosylates itself and other proteins. PARP facilitates DNA repair complex formation, e.g., with...

Multicellular organisms must have means of preserving their genomic integrity or face catastrophic consequences such as uncontrolled cell proliferation or massive cell death. One response is a modification of nuclear proteins by the addition and removal of polymers of ADP-ribose that modulate the properties of DNA-binding proteins involved in DNA repair and metabolism. These ADP-ribose units ar...

Purpose:PARP inhibitors are beingdeveloped as therapeutic agents for cancer.More than six compounds have entered clinical trials. The majority of these compounds are b-nicotinamide adenine dinucleotide (NADþ)-competitive inhibitors. One exception is iniparib, which has been proposed to be a noncompetitive PARP inhibitor. In this study, we compare the biologic activities of two different structu...

Novel poly(ADP-ribose)polymerase (PARP)-1 inhibitors containing, the 4-(benzylideneamino)-N-(quinolin-8-yl)benzamide moiety, were designed and synthesized. The docking study revealed that compounds possess significant to moderate interaction with targeted enzyme PARP1. Among them compound 3d (−52.04 K/cal) 3e (−50.234 showed similar Glidescore compared Olaprib (−57.76 K/cal). Some of synthesize...

Submit Manuscript | http://medcraveonline.com Abbreviations: PCa: Prostate Carcinoma; CRPC: Castrationresistant Prostate Carcinoma; MMR: Mismatch Repair; ADT: Androgen-deprivation Therapy; OS: Overall Survival; NER: Nucleotide Excision Repair; BER: Base Excision Repair; HDR: Homology Directed Repair; HR: Homologous Recombination; DDR: DNA Damage Response; NHEJ: Non-homologous End Joining; SSB: ...

Glycemic control is the primary mediator of diabetic microvascular complications and also contributes to macrovascular complications. A new study (see related article beginning on page 1049) reveals a previously unrecognized association between oxidant activation of poly(ADP ribose) polymerase (PARP) and upregulation of known mediators of glycemic injury. Inhibitors of PARP may have potential t...

Background: Drug metabolites are generally more soluble, achieve lower concentrations in human plasma and can be excreted easily than their parent drugs. Accordingly, drug rarely characterized comprehensively preclinical models on- off-target activity is often overlooked. However, play significant roles the efficacy safety of dugs help us explain clinical observations. Four PARP inhibitors have...

Inhibitors of poly (ADP-ribose)-polymerase-1 (PARP) are highly lethal to cells with deficiencies in BRCA1, BRCA2 or other components of the homologous recombination pathway. This has led to PARP inhibitors entering clinical trials as a potential therapy for cancer in carriers of BRCA1 and BRCA2 mutations. To discover new determinants of sensitivity to these drugs, we performed a PARP-inhibitor ...

Alkylating agents are commonly used to treat cancer. Although base excision repair (BER) is a major pathway for repairing DNA alkylation damage, under certain conditions, the initiation of BER produces toxic repair intermediates that damage healthy tissues. The initiation of BER by the alkyladenine DNA glycosylase (AAG, a.k.a. MPG) can mediate alkylation-induced cytotoxicity in specific cells i...