Various molecular mechanisms of the acquired resistance have been clarified. This chapter describes the synthetic lethal mechanism of PARP inhibitors, the mechanism of acquired resistance to PARP inhibitors, and the development of various PARP inhibitors.Sunada, Shigeaki...
PARP: Mechanism of action PARP is a family of 17 intracellular enzymes associated with the cellular stress response, chromatin remodeling, DNA repair, and apoptosis [165]. In general, PARPs mediate reversible posttranslational modification via synthesis of nucleic acid mimic molecules known as poly-AD...
The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings. Molecular oncology 2011; 5: 387-93. 【11】Burkle A, Virag L. Poly(ADP-ribose): PARadigms and PARadoxes. Molecular Aspects of Medicine 2013; 34: 1046-65. 【12】Shen Y, Rehman FL, Feng Y...
Mechanism of action and pharmacology of PARP inhibitors A number of PARP inhibitors are under clinical development: rucaparib (CO-338; AG014699, PF-0367338; oral/IV), iniparib (BSI-201), olaparib (AZD-2281; oral), veliparib (ABT-888; oral), MK-4827, BMN-673, CEP-9722 (oral) and E...
PARP trapping represents an additional mechanism of action for PARPi, and there are preclinical data to suggest that the consequences of trapped PARP–DNA complexes are actually more cytotoxic than the unrepaired SSBs that initially result from the loss of PARP activity [20]. Though preclinical ...
This review mainly introduces the concept of synthetic lethality and homologous recombination, describes the mechanism of action of PARP inhibitors within this concept, discusses problems such as resistance, enumerates the current progress and achievements of clinical trials for PARP inhibitors in pancreatic...
Mechanism of action and pharmacology of PARP inhibitors A number of PARP inhibitors are under clinical development: rucaparib (CO-338; AG014699, PF-0367338; oral/IV), iniparib (BSI-201), olaparib (AZD-2281; oral), veliparib (ABT-888; oral), MK-4827, BMN-673, CEP-9722 (oral) and E...
This review summarizes current insights into the mechanism of action ofPARP inhibitors, its recent clinical trials, and potential next steps in the evaluation of this promising class ofanti-cancer drugs.Keywords: Poly (ADP-ribose) polymerases, Nicotinamide, RucaparibFindingsPoly (ADP-ribose) ...
According to Pommier, these results indicated that olaparib must have additional modes of action, and their detailed cellular analyses identified a critical one: olaparib was trapping PARP proteins, specifically PARP1 and PARP2, at sites ofDNA damage, and the trapped PARP protein-DNA complexes were...
Small-molecule inhibitors of PARP are thought to mediate their antitumor effects as catalytic inhibitors that block repair of DNA single-strand breaks (SSB). However, the mechanism of action of PARP inhibitors with regard to their effects in cancer cells is not fully understood. In this study, ...