Ask about this productRelated genes to: PARP2 antibody
- Gene:
- PARP2 NIH gene
- Name:
- poly(ADP-ribose) polymerase 2
- Previous symbol:
- ADPRTL2
- Synonyms:
- -
- Chromosome:
- 14q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-24
- Date modifiied:
- 2015-11-06
Related products to: PARP2 antibody
Related articles to: PARP2 antibody
- Niraparib is a potent, orally bioavailable inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, specifically targeting PARP-1 and PARP-2 to induce selective cytotoxicity in malignancies by disrupting DNA repair mechanisms. Given that the S-niraparib exhibits significantly higher pharmacological activity than the R-isomer, the development of a precise analytical technique to ensure enantiomeric purity is a critical requirement for pharmaceutical quality control. This study details the development and validation of a stability-indicating chiral high-performance liquid chromatography (HPLC) method for the quantitative assessment of enantiomeric purity content. Separation was successfully achieved using a Chiralpak AS-H 250 × 4.6 mm, 5 μm column under isocratic conditions with a mobile phase consisting of n-hexane, ethanol, methanol, and diethylamine in a 750:100:150:1.0 (v/v/v/v) ratio. The system was operated at a flow rate of 0.7 mL/min and a controlled column temperature of 40°C, with detection monitored via a UV/visible detector at 240 nm. The method was rigorously validated in accordance with ICH Q2(R2) guidelines, demonstrating specificity, accuracy, and precision. A resolution factor of greater than 2.0 was maintained between niraparib and its isomer. Analytical sensitivity was established through the determination of the limit of detection (LOD) and limit of quantitation (LOQ) using signal-to-noise ratios of 3 and 10, respectively, with a 1 mg/mL sample concentration and a 10 μL injection volume. Calibration curves proved linear over the studied range, confirming the method's reliability. The results indicate that this stability-indicating approach is highly effective for routine in-process quality control, batch release testing, and long-term stability monitoring of niraparib drug substances. - Source: PubMed
Kondaveti Praveen KumarDouglas PaulRaghunadh AkulaKalyanaraman L - Poly(ADP-ribose) polymerases (PARPs) play a central role in maintaining genome stability and catalyzing the transfer of ADP-ribose units from NAD to target proteins through a process known as poly(ADP-ribosyl)ation (PARylation). While mammalian PARPs are extensively characterized, their plant homologues remain less explored. Here, we dissect the mechanistic regulation of PARP2 (atPARP2) through its interactions with DNA and poly(ADP-ribose) (PAR). Biolayer interferometry (BLI) binding studies revealed that atPARP2 recognizes phosphorylated DNA double-strand breaks (p-DSBs) and PAR with a nanomolar affinity. Using the SAP domain of atPARP2, we reported for the first time that it binds both PAR and p-DSBs, thereby significantly enhancing the binding affinity of atPARP2 for PAR and p-DSBs. In addition, isothermal titration calorimetry (ITC) and biochemical assays demonstrated that PAR serves as an allosteric activator of atPARP2, with the WGR domain acting as a key module for PAR binding. Enzymatic assays further established the indispensable role of SAP domains in enhancing DNA- and PAR-dependent catalytic activities. Together, our findings demonstrate that atPARP2 may employ a modular strategy, integrating DNA break sensing and PAR recognition, to fine-tune its catalytic function in response to genotoxic stress. - Source: PubMed
Publication date: 2026/06/11
Greeshma Shanavas PHanuman Dagur SinghRajakumara Eerappa - Purines are essential bioactive molecules that interact with a large fraction of the human proteome. Despite their importance, the scope of actionable purine-binding pockets for ligand discovery remains limited. Here, we develop a quantitative chemoproteomics platform using sulfonyl-purine (SuPUR) chemistry to produce a massive and functional map of the human purine interactome. The SuPUR platform captures 31,000+ targetable tyrosine and lysine sites, representing the most comprehensive beyond cysteine chemoproteomics database for enabling protein ligand discovery. SuPUR ligands that bind through a regioselective fashion serve as enabling starting points for developing potent (nanomolar) and proteome-wide-selective modulators of enzymatic and protein-protein interaction function. Phenotypic screening identifies a site-specific (Y237) and regioselective SuPUR ligand of ACAT2 to reveal an unexpected metabolic dependency in cancer cells. A crystal structure of SuPUR ligand-bound ACAT2 reveals the purine group binds deep in the CoA pocket forming key interactions with catalytic residues via a water bridge to guide future structure-based ligand design. - Source: PubMed
Publication date: 2026/06/05
Li ZhihongTsai Hsiao-KueiLibby Adam HFounds Michael WMurtagh Olivia LWare Madeleine LLeace David MWolfe Wesley JGingrich Phillip WAl-Lazikani BissanChang Chin-YuanHsu Ku-Lung - Parkinson's disease (PD) is closely associated with PARP1 overactivation. Although our previously developed compound HM568 has been shown to alleviate PD pathology, its mechanism of action remained unknown. In this study, we show that HM568 significantly improves behavioral deficits, prevents the loss of dopaminergic neurons, and restores blood-brain barrier integrity and mitochondrial morphology in MPTP/MPP-induced PD models. Proteomic analysis then indicated that the effects of HM568 were enriched in mitochondrial respiratory chain complexes. Building on this clue, we confirmed in cellular models that HM568 counteracts MPP-induced inhibition of complexes I, III, and IV, thereby restoring mitochondrial function. Further mechanistic exploration uncovered that HM568 acts by elevating intracellular NAD levels, downregulating PARP1 protein expression, and inhibiting its enzymatic activity. Molecular docking indicated a high binding affinity between HM568 and PARP1 (-10.38 kcal/mol). Molecular dynamics simulations provided structural insights into HM568's selective inhibition advantage for PARP1 over PARP2. Our study demonstrates that HM568 corrects mitochondrial dysfunction and energy metabolism imbalance possibly through inhibition of PARP1 and modulation of NAD⁺ metabolism, providing a mechanistic foundation for its potential as a therapeutic agent for Parkinson's disease. - Source: PubMed
Publication date: 2026/06/05
Li MinpengLi WeiLiu YingjieFu TingyuanPeng KaiyeWang ChangmeiZhang JingFeng YifanWu Xia - The use of PARP inhibitors (PARPi) has profoundly changed the treatment of BRCA1/BRCA2-mutated cancers. Despite this, acquired resistance to PARPi has become a major challenge in the clinic. Hence, a more detailed understanding of the mechanisms underlying PARPi sensitivity is crucially needed. Here, we show that loss of the alternative clamp loader complex CHTF18-RFC2/5 leads to a remarkable sensitization to PARPi. Loss of CHTF18 is not associated with defective RAD51 foci formation excluding a defect in homologous recombination. On the contrary, treatment with PARPi triggers replicative gap accumulation in CHTF18 knockout (KO) cells. By performing transient silencing experiments, we highlight PARP1-PARP2 trapping at replicative gaps as a major determinant of sensitivity to these compounds. Crucially, loss of 53BP1 does not rescue PARPi sensitivity in CHTF18 KO cells, outlining Polε and the CHTF18-RFC2/5 complex as potential novel targets for cancer therapeutics. - Source: PubMed
Publication date: 2026/06/03
Buckley-Benbow LaurynOzgencil MeryemTardocchi AlessiaAgnarelli AlessandroBellelli Roberto