Ask about this productRelated genes to: TDP1 antibody
- Gene:
- TDP1 NIH gene
- Name:
- tyrosyl-DNA phosphodiesterase 1
- Previous symbol:
- -
- Synonyms:
- FLJ11090, SCAN1
- Chromosome:
- 14q32.11
- Locus Type:
- gene with protein product
- Date approved:
- 2002-07-13
- Date modifiied:
- 2008-08-11
Related products to: TDP1 antibody
Related articles to: TDP1 antibody
- Cervical cancer remains a major global threat to women's health. Topotecan (), a topoisomerase I (TOP1) inhibitor, is widely used for advanced or recurrent disease; however, its efficacy is compromised by tyrosyl-DNA phosphodiesterase 1 (TDP1)-mediated DNA repair. Moreover, effective TDP1 inhibitors remain limited. In this study, we modified the lead compound based on the 6H-benzimidazo[1',2':1,2]pyrido[3,4-]indole scaffold to synthesize derivatives. Derivative exhibited the most potent TDP1 inhibitory activity (IC = 1.52 ± 0.34 μM). Molecular docking and dynamics simulations revealed that simultaneously occupied TDP1's catalytic and DNA-binding domains. Furthermore, synergized with to suppress HeLa cell proliferation. This effect was likely mediated by enhanced DNA damage, induced apoptosis, S-phase cell cycle arrest, and potentially ferroptosis. In vivo, the combination treatment significantly inhibited tumor growth in cervical cancer xenograft models. These findings identify as a promising TDP1 inhibitor with potential to enhance TPT-based therapy. - Source: PubMed
Publication date: 2026/04/21
Zeng HuangQiu BoYang JiunlongXie YumanHuang HuiZhang ShengyuanNie HuaWang NanHuang ZeyongWu LingfengLiu JiayaoZheng XuerouZhuang YuanbeiYang Hao - Overcoming drug resistance in pancreatic ductal adenocarcinoma (PDAC) remains a major challenge due to dense fibrotic stroma, DNA repair-mediated resistance, drug efflux mechanisms, and an immunosuppressive tumor microenvironment (TME). Here, we use photoactivatable multi-inhibitor liposomes (PMILs) as a clinically translatable strategy to immunomodulate and enhance PDAC treatment using FDA-approved agents: minocycline for tumor priming by downregulating Tdp1, benzoporphyrin derivative incorporated into the liposomal bilayer for photodynamic priming (PDP) of the microenvironment, and irinotecan (IRI) for cytotoxicity. PMILs enable light-triggered PDP followed by IRI release. The reduced Tdp1 combined with PDP and IRI acts synergistically to enhance antitumor activity. In an orthotopic PDAC mouse model, dual priming significantly increased intratumoral IRI accumulation while downregulating Tdp1 and ABCG2, two key mediators of IRI resistance. These effects were augmented by immune activation, including increased CD8T-cell infiltration, reduced regulatory T cells, and M2-like macrophage population. This combination achieved sustained local tumor regression, abscopal effects in untreated distant tumors, and a significant improvement in long-term survival (63%). By integrating clinically approved agents with non-overlapping mechanisms within a light-activated delivery platform, this approach enhances IRI efficacy, reprograms the TME, and promotes antitumor immunity, offering a translatable strategy to sensitize PDAC to chemo- and immunotherapy. - Source: PubMed
Publication date: 2026/04/17
Cabral Fernanda VQuilez-Alburquerque JoseMooradian OliviaVytheswarran ShivendranParshad BadriObaid GirgisHuang Huang-ChiaoHasan Tayyaba - Neohesperidin dihydrochalcone (NHDC) has been confirmed to possess excellent nutritional activities as a natural flavonoid low-calorie sweetener, but its practical application in the food industry was greatly limited due to its low water solubility. The potential NHDC activity against oxidative stress (OS) diseases was explored through network pharmacology and molecular docking technology, and a highly water-soluble NHDC-L-arginine complex (NL) was prepared by combining NHDC with L-arginine to overcome this technical bottleneck. Meanwhile, the enhancement of antioxidant capacity markers under non-stressed conditions following NL treatment was systematically investigated in (), and transcriptomic and metabolomic analyses were integrated to reveal the potential regulatory mechanism at the molecular and metabolic levels. It was found that NHDC could exert potential anti-OS effects by targeting and binding to key proteins such as CYP19A1, TYR, EPHX2, TDP1, ESR1, and SLC5A1. In addition, the MDA level in after NL intervention was significantly reduced to 0.65 ± 0.06 nmol/mg prot, while the activities of antioxidant enzymes T-SOD, GSH-Px, and CAT were significantly increased to 48.83 ± 1.75 U/mg prot, 112.95 ± 0.55 U/mg prot, and 6.30 ± 0.16 U/mg prot, respectively. Longevity regulating pathway-worm was identified as a potential key signaling pathway for NL to regulate the enhancement of antioxidant capacity markers under non-stressed conditions of at the molecular level, and the pentose phosphate pathway was the core metabolic pathway. These results could offer theoretical support for the potential development of NHDC and NL in the field of antioxidants, as well as their large-scale applications in the functional food and flavored food industries. - Source: PubMed
Publication date: 2026/04/04
Chen PingZhu SimingTian MenghanWang YutaoChen LiangWang Zhendong - Class switch recombination (CSR) and somatic hypermutation are essential mechanisms of effective antibody production, dependent on the enzyme activation-induced cytidine deaminase (AID). Since AID lacks the intrinsic ability to cleave DNA, topoisomerase 1 (TOP1) has been hypothesized to mediate AID- and transcription-dependent DNA cleavage. However, the molecular mechanism underlying the formation of an irreversible TOP1-DNA cleavage complex (TOP1-CC) following cytidine to uridine (C-to-U) editing by AID remains undefined. To unveil this mechanism, we tested antisense oligonucleotides (ASOs) targeting noncoding germline transcripts (GLTs) that form R-loops across DNA cleavage sites during CSR. These studies revealed that the anti-GLT-ASOs increased DNA cleavage frequency, concomitant with a decrease in R-loops. Mechanistically, ASO-mediated R-loop disruption led to increased TOP1-CC formation specifically within the GLT region during CSR. Furthermore, an in vitro transcription assay demonstrated that RNase H-mediated R-loop degradation enhanced positive supercoiling and double-strand breaks in the presence of TOP1, even in the absence of AID. Moreover, knockout of Tyrosyl-DNA phosphodiesterase 1 (), a canonical TOP1-CC processing enzyme, revealed that TDP1 suppresses CSR, indicating that accumulated TOP1-CCs in knockout cells serve as substrates for CSR through an alternative TOP1-CC processing pathway. Collectively, these results suggest the R-loop destabilization as a critical, hitherto unrecognized intermediary step linking C-to-U editing to TOP1-CC formation. AID-mediated C-to-U editing within R-loops introduces a G:U wobble base pair, which we hypothesize renders R-loops unstable and sensitive to nuclear RNases, leading to R-loop disruption; this disruption consequently induces the TOP1-CCs and results in CSR, as confirmed in this study. - Source: PubMed
Publication date: 2026/04/03
Kobayashi MakiChen XiHonjo Tasuku - Tyrosyl-DNA phosphodiesterase I (Tdp1) hydrolyzes 3'- and 5'-phosphodiester linked DNA-adducts, including Topoisomerase I- and II-DNA covalent complexes (Topo1cc and Topo2cc). Utilizing the model organism Saccharomyces cerevisiae, which only expresses Tdp1 and does not contain TDP2 orthologs or activity, we investigated the conditions under which Tdp1 processes Topo2(peptide)cc in cells and examined the role of the Tdp1 N-terminal domain in resolving Topo2(peptide)cc. We replaced the transcription activator PDR1 gene with the chimeric pdr1dbd-CYC8 transcription repressor in our strain, resulting in increased sensitivity to etoposide and doxorubicin but not to mitoxantrone. Using Tdp1 catalytic histidine mutants that induce substrate-dependent toxicity, we detected that Tdp1 selectively processes etoposide stabilized Topo2(peptide)cc. In contrast, Tdp1's processing of Topo1cc is drug independent. Moreover, we observed that the yeast SCAN1-like H432R mutant induces a more severe toxic phenotype when processing etoposide-Topo2(peptide)cc than Topo1cc with or without camptothecin. Extrapolating this observation to SCAN1 cerebellar neurons, we hypothesize that the contribution of Tdp1H493R processing of Topo2β(peptide)cc trapped by e.g., oxidative damaged nucleotides, is potentially more substantial towards cerebellar atrophy and compels further investigation. Nonetheless, the observed toxic phenotypes induced by Tdp1 mutants are recessive and suppressed by endogenous wild-type Tdp1 by lowering 5'Tdp1(mutant)cc. Moreover, Tdp1 cannot process etoposide-Topo2cc in cells without its N-terminal domain. This suggests that in cells Tdp1's N-terminal domain plays a critical role in regulating Tdp1 activity potentially by mediating recruitment to the DNA-adduct and/or facilitating accessibility to the phosphodiester linkage within a protein/peptide-DNA complex or stabilizing of the DNA strands related to damaged nucleotide-adducts. - Source: PubMed
Publication date: 2026/03/17
Albertson Victoria MMusani Aasim MBridges Leanna GSegura Isaac Avan Waardenburg Robert C A M