AG14361 is a potent oly(ADP-ribose) polymerase-1 inhibitor (human PARP-1 Ki = 5.8 nM) that suppresses 25 μM MNNG-induced PARP-1 activity (NAD+ depletion = 70% without vs.12% with 0.4 μM AG14361; 87% reduced ADP-ribose polymer induction with 0.4 μM AG14361) and greatly amplifies temozolomide and topotecan cytotoxicity (2.2- and 2.0-fold lower IG50, respectively, with 0.4 μM AG14361) in A549 cultures. AG14361 is shown to selectively kill BRCA2-deficient cells over BRCA2-expressing cells both in cultures (1-10 μM) and in mice in vivo (25 mg/10 mL/kg/d ip).
Potent poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor in vitro and in vivo.
Despite continuous improvements in treatment of glioblastoma, tumor recurrence and therapy resistance still occur in a high proportion of patients. One underlying reason for this radioresistance might be the presence of glioblastoma cancer stem cells (GSCs), which feature high DNA
High-mobility group box 1 (HMGB1) exhibits various functions according to its subcellular location, which is finely conditioned by diverse post-translational modifications, such as acetylation. The nuclear HMGB1 may prevent from cardiac hypertrophy, whereas its exogenous protein is proven to induce
Poly(ADP-ribose)polymerases (PARPs) are a family of NAD+ consuming enzymes that play a crucial role in many cellular processes, most clearly in maintaining genome integrity. Here, we present an extensive analysis of the alteration of mitochondrial morphology and the relationship to
Molecular cancer therapeutics, 17(10), 2206-2216 (2018-07-05)
Parp inhibitors (Parpi) are commonly used as single agents for the management of tumors with homologous recombination repair (HRR) deficiencies, but combination with radiotherapy (RT) is not widely considered due to the modest radiosensitization typically observed. BMN673 is one of
Poly(ADP-ribose) polymerase (PARP1) facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Nevertheless, PARP1-/- mice are viable, fertile and do not develop early onset tumours. Here, we show that PARP inhibitors
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