PARP12 Blocking Peptide, Blocking Peptides
- Known as:
- PARP12 Blocking Peptide, Blocking Peptides
- Catalog number:
- 33R-3134
- Product Quantity:
- 100 ug
- Category:
- -
- Supplier:
- Fitzgerald
- Gene target:
- PARP12 Blocking Peptide Peptides
Related genes to: PARP12 Blocking Peptide, Blocking Peptides
- Gene:
- PARP12 NIH gene
- Name:
- poly(ADP-ribose) polymerase family member 12
- Previous symbol:
- ZC3HDC1
- Synonyms:
- FLJ22693, PARP-12, ZC3H1
- Chromosome:
- 7q34
- Locus Type:
- gene with protein product
- Date approved:
- 2003-12-10
- Date modifiied:
- 2015-11-06
Related products to: PARP12 Blocking Peptide, Blocking Peptides
Related articles to: PARP12 Blocking Peptide, Blocking Peptides
- Since the identification of PARP1/2 as synthetic lethal targets in BRCA-deficient breast cancer and the subsequent approval of catalytic domain-targeting PARP inhibitors, the landscape of PARP inhibitors has expanded to encompass a broader chemical tool kit. Beyond PARP1/2's canonical role in DNA repair, PARP inhibitors have revealed context-dependent PARP functions in anticancer immunity, viral infection, neurodegeneration, and cellular organization. These discoveries have motivated new strategies that extend past targeting catalytic domains. In this review, we highlight three emerging directions: () biological insights revealed by PARP1/2 inhibitors in oncology and other settings, () progress in developing inhibitors against PARP family members beyond PARP1/2, and () approaches that target noncatalytic domains or modulate PARP function through mechanisms such as interface disruption and targeted degradation. We conclude by outlining key next steps for advancing PARP pharmacology, including substrate mapping, utilizing rational polypharmacology, targeting ADP-ribose readers and erasers, and expanding structural coverage of PARP family proteins. - Source: PubMed
Publication date: 2026/08/10
Owens Michael CLeung Anthony K L - Talazoparib (TZ) is a potent poly(ADP-ribose) polymerase 1/2 (PARP1/2) inhibitor that uniquely traps PARP complexes at sites of single-strand DNA damage thereby offering opportunities for targeted radioligand therapy. Radiolabeled halogenated TZ derivatives were synthesized using boronic ester precursors to enable incorporation of diagnostic and therapeutic radionuclides: F for PET imaging, Br for Auger electron radiotherapy, and At for targeted alpha radiotherapy. Copper-mediated radio-halogenation afforded racemic F-TZ, Br-TZ, and At-TZ in sufficient radiochemical yields (4.3 ± 2.6%, = 33; 29.0 ± 12.0%, = 4; 3.6 ± 3.8%, = 9, respectively), ∼99% radiochemical purity and proven stability under formulation conditions. Molecular dynamics simulations of halo-TZ derivatives predicted an inverse relationship between halogen size and PARP1 binding affinity. Indeed, cell uptake of radio-halogenated TZ analogues indicated selective uptake in a panel of cell types that correlated with PARP1 levels but was inversely related to the atomic radii of the halogen series. Despite modest specific activity and specific uptake, Br-TZ showed significant cytotoxicity. Further investigation of F-TZ with Br-TZ as a radiotheranostic pair will be facilitated by the synthetic schemes herein. - Source: PubMed
Publication date: 2026/07/27
Muzzioli RiccardoPisaneschi FedericaGammon Seth TSutton Margie NNapoli AriannaPuglielli Raffaele BelliniMcIntosh LaurenTereshatov EvgenyTabacaru GabrielSchultz StevenMcCann LauraBurns Jonathan DYennello SherryPiwnica-Worms David - PARP1 is a key regulator of genome integrity, DNA repair, and epigenetic control. PARP inhibitors (PARPis), designed as nicotinamide mimetics that target the NAD⁺ binding pocket, exploit synthetic lethality in homologous recombination-deficient tumors and have been approved for the treatment of multiple cancers. - Source: PubMed
Publication date: 2026/07/17
Sharma MuskanByran GowrammaBalachandran HardhaRajagopal Kalirajan - Targeting replication-associated DNA repair mechanisms, including the control of ADP-ribosylation by PARP1/2 and PARG, is a powerful therapeutic approach for cancer. However, the mechanisms by which PARG inhibition impacts DNA replication remain unclear. Here, we combine isolation of proteins on nascent DNA (iPOND) with quantitative proteomics and functional assays to investigate replication fork dynamics upon acute PARG inhibition. We find that FET family proteins (FUS, EWS, and TAF15) are recruited to replication forks in a PAR-dependent manner, forming condensates that slow fork progression and promote fork reversal. FET proteins control fork dynamics in response to some, but not all, replication stresses. FUS inactivation leads to unrestrained fork progression via RECQ1 and PRIMPOL, increased single-stranded DNA gaps, genome instability, and synthetic lethality with BRCA1 deficiency. These findings reveal that FET protein assemblies modulate replication stress responses, influencing genome stability and the cellular response to cancer therapeutics targeting PARylation pathways. - Source: PubMed
Publication date: 2026/06/30
Giansanti CelesteSchultz Jack CJackson JessicaVindigni AlessandroCortez David - PARP1/2 inhibitors (PARPi) are effective in cancer therapy due to their synthetic lethality in cells with defects in DNA double-strand break repair (DSBR). Here, we show that DSBR-proficient, naïve pluripotent mouse embryonic stem cells (mESC) exhibit high sensitivity towards PARP1/2 inhibition by talazoparib and olaparib. This sensitivity results from a two-tiered response of mESC to PARPi, starting with the activation of DNA stress signalling via ATM and followed by a p53-controlled, TET-TDG-dependent transcriptional response, including the de-repression of endogenous retroviral elements (ERVs). The resulting accumulation of double-stranded RNAs then elicits hallmarks of viral mimicry, marked by induction of type I interferon and necroptosis responses, alongside caspase activation. Accordingly, depletion of p53, TET, or TDG confers PARPi resistance in mESC. These findings highlight active DNA demethylation as a critical mediator of PARPi sensitivity in mESC and provide mechanistic insight into how DNA stress drives ERV expression in cells with accessible chromatin. - Source: PubMed
Xu JianmingSchwarz Simon DGunasekera KapilaSteinacher RolandKuśnierczyk AnnaHottiger Michael OSchär Primo