PARP2 Assay Kit
- Known as:
- PARP2 Assay Kit
- Catalog number:
- 80552
- Product Quantity:
- 100 reactions
- Category:
- Peptides
- Supplier:
- BPS Bioscience
- Gene target:
- PARP2 Assay Kit
Related genes to: PARP2 Assay Kit
- 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
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- Dual inhibition of Polθ and PARP1 represents a promising precision therapy strategy for HR-deficient tumors. While our first-generation Polθ/PARP1 dual inhibitor 4 provided proof-of-concept, its further development was hampered by poor selectivity over PARP2 and metabolic instability. Herein, we describe a structure-guided optimization that pioneers the integration of PARP1-selective pharmacophores. This effort culminated in the discovery of compound PP-048 (23), a second-generation dual inhibitor with single-digit nanomolar potency against Polθ and PARP1 (IC50 = 4.9 nM and 6.8 nM, respectively) and >226-fold selectivity over PARP2, PARP3, PARP5a/b, and PARP7. Notably, PP-048 displayed markedly improved hepatic stability and favorable oral systemic exposure. In an MDA-MB-436 xenograft model, PP-048 (10 mg/kg) achieved marked tumor growth inhibition (TGI = 91%) without eliciting the hematologic toxicity associated with PARP2 inhibition. To our knowledge, PP-048 represents the first reported PARP1-isoform-selective dual inhibitor, establishing a strategic foundation for development of this emerging class of inhibitors. - Source: PubMed
Ma LuyuZhong MingzheChang YingxuanLuo MingjinLiu XinyanGe XiaofanXu SitianZhang YunLiu ZiyeXiang HuaLuo Guoshun - Ovarian cancer remains a leading cause of gynecologic cancer-related deaths worldwide. Deficiencies in BRCA1/2 are well-established biomarkers that predict sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). However, emerging evidence indicates that a subset of BRCA-proficient tumors also responds to PARPi therapy, suggesting the presence of additional molecular mechanisms. We hypothesized that the composition of the PARP1 protein complex and PARylation-mediated signaling contribute to PARPi response in BRCA-proficient HGSOC. We assessed PARPi response across a panel of BRCA-proficient ovarian cancer cell lines and identified distinct sensitive and resistant groups. Chemical proteomics with rucaparib revealed different PARP1 complexes including higher enrichment of MSH6 in sensitive cells. Co-immunoprecipitation analyses further confirmed differential assembly of PARP1-MSH6-PARP2 complexes between sensitive and resistant models. To explore PARylation signaling, we performed ADP-ribosylation proteomics using clickable NAD⁺ analogs, revealing distinct PARylation profiles between sensitive and resistant cell lines. CHAF1A, a known MSH6 interactor and PARP1 substrate, showed more pronounced reduction in ADP-ribosylation in PARPi-sensitive cells. Targeting MSH6 using CRISPR or siRNA decreased PARPi sensitivity. In addition, mTOR signaling was reduced in sensitive, but increased in resistant cells, following rucaparib treatment. Notably, MSH6 knockdown led to increased CHAF1A expression regardless of rucaparib treatment. Importantly, knockdown of CHAF1A significantly impaired cell viability, especially in A2780 cells, and suppressed mTOR signaling, suggesting that CHAF1A acts downstream of MSH6 to regulate the mTOR axis. Furthermore, co-treatment with mTORC1 inhibitors enhanced the cellular effects of rucaparib in resistant cells, suggesting a therapeutic potential of targeting downstream mTOR effectors to overcome intrinsic resistance. In conclusion, this study identifies the PARP1-MSH6 interaction to modulate PARPi sensitivity via CHAF1A-mTOR signaling in BRCA-proficient ovarian cancer. By integrating chemical proteomics and ADP-ribosylation proteomics, we delineate the interplay between PARP1 complex composition and signaling dynamics, highlighting MSH6 as a critical modulator of PARPi response and potential biomarker to enhance therapeutic efficacy in BRCA-proficient HGSOC. - Source: PubMed
Publication date: 2026/09/02
Deng OuNepomuceno Thales Da CostaFang BinWelsh Eric AIzumi VictoriaMartin Rachael HGeorge Erin MKoomen John MMonteiro Alvaro NRix Uwe - Poly (ADP-ribose) polymerase-1 (PARP-1) is a key regulator of DNA repair, genomic stability, and programmed cell death. PARP-1 inhibition induces synthetic lethality in homologous recombination-deficient tumors, particularly those with BRCA mutations. Firstgeneration PARP inhibitors, including Olaparib, Niraparib, Talazoparib, and Rucaparib, have significantly advanced targeted cancer therapy but are limited by toxicity, resistance, and off-target effects. This review aims to highlight the potential of heterocyclic scaffolds for developing selective and improved PARP-1 inhibitors, with emphasis on structure-activity relationships and optimization strategies. - Source: PubMed
Publication date: 2026/08/06
Balachandran HardhaByran GowrammaKarri Veera Venkata Satyanarayana ReddyMurugesan Senthil KumarRajagopal Kalirajan - The anterior pituitary integrates endocrine regulation, cellular growth, and adaptive responses. Adipokines, secreted mainly by adipose tissue, act as hormonal signals linking metabolism, inflammation, appetite, and reproduction. They regulate hypothalamic-pituitary-ovarian axis by modulating hormone secretion and intracellular signaling. The presence of adipokine receptors in anterior pituitary suggests local metabolic-endocrine interactions. Omentin-1, predominantly expressed in visceral adipose tissue, participates in glucose metabolism and ovarian steroid regulation. Recent findings indicate that omentin-1 modulates tropic hormones, their receptors, and adipokine balance in anterior pituitary cells. We hypothesized that omentin-1 affects protein expression and signaling pathways involved in pituitary cell proliferation and apoptosis. This study examined its effects in anterior pituitary cells from Large White and Meishan pigs. Proteomic analysis identified 230 candidate differentially abundant proteins after omentin-1 treatment: 30 downregulated and 3 upregulated in Large White pigs, and 107 downregulated and 90 upregulated in Meishan pigs, associated with enriched 116 Gene Ontology terms. Key proteins were associated with cell cycle, DNA replication, gene expression, and posttranscriptional/posttranslational regulation. Responses differed between breeds. CDK5RAP2 and SIX1 were linked to proliferative control in Large White pigs, whereas AKT1S1 and RHOA were among the proteins associated with the broader proteomic response observed in Meishan pigs. Meishan pigs showed dynamic apoptotic protein regulation, including HTRA2, PARP2, and DFFA. Complementary in vitro experiments demonstrated that omentin-1 downregulated cyclins and caspase-3, upregulated BCL2, increased BCL2/BAX ratio, and modulated ERK1/2, AKT, AMPKα, and STAT3 phosphorylation. Together, these findings suggest that omentin-1 modulates proteomic networks and intracellular signaling associated with anterior pituitary cell function during the mid-luteal phase of the estrous cycle. - Source: PubMed
Publication date: 2026/08/19
Respekta-Długosz NataliaKubicka KarolinaGreggio AleksandraŚwiderska BiankaMalinowska AgataRytelewska EdytaOpydo MałgorzataDupont JoëlleKamiński TadeuszSmolińska NinaRak Agnieszka - Developing highly selective PARP1 inhibitors is a promising strategy to improve the therapeutic window compared with dual PARP1/2 inhibitors. Through structure-guided design and optimization, we developed (R)-A17, a novel, highly selective PARP1 inhibitor featuring a unique tricyclic scaffold. It demonstrates nanomolar enzymatic potency (PARP1 IC50 = 2.4 nM), exceptional 65.8-fold selectivity over PARP2, and robust antiproliferative activity in BRCA-deficient cells. (R)-A17 exhibits favorable pharmacokinetic properties with complete oral bioavailability (F = 100%) in mice. Mechanistically, it selectively inhibits PARP1-mediated PARylation and induces DNA damage and G2/M phase arrest. In vivo, oral administration of (R)-A17 produced dose-dependent antitumor efficacy in BRCA mutant xenograft models, achieving tumor growth inhibition values of 57.8, 86.3, and 91.3% at doses of 0.3, 1, and 3 mg/kg, respectively, while also synergizing effectively with liposomal irinotecan in an HCT116 xenograft model. These results establish (R)-A17 as a promising candidate and validate the design strategy for the next-generation PARP1-targeted therapy. - Source: PubMed
Guo ZhongningSun RongrongYang LinyuZou YurongGuo TaoMa ZiyanLiu ShuaiWang PengYuan YongtingYe LingpingChen YonglinQin SonghuiLi NaBai PengYuan QuanYan WeiBo WeichenWang TaijinHu JiankunChen Lijuan