Human TDP1 cDNA Clone
- Known as:
- Human TDP1 complementary Desoxyribonucleic acid Clone
- Catalog number:
- DC01854
- Category:
- -
- Supplier:
- Abgen
- Gene target:
- Human TDP1 cDNA Clone
Related genes to: Human TDP1 cDNA Clone
- 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: Human TDP1 cDNA Clone
Related articles to: Human TDP1 cDNA Clone
- Tyrosyl-DNA phosphodiesterase I (TDP1) repairs topoisomerase I (TOP1)-mediated DNA damage and is a promising anticancer target, particularly in combination with TOP1 inhibitors. However, the discovery of potent and drug-like TDP1 inhibitors remains challenging due to the limited structural diversity of known active compounds. Here, we developed an integrated computational framework combining machine learning (ML), deep learning (DL), and structure-based docking with experimental validation. A curated dataset of 2040 compounds (857 active, 1183 inactive) was assembled and analyzed by scaffold composition. A total of 40 binary classification models were constructed using six ML algorithms and a deep neural network (DNN), each paired with five molecular fingerprint representations, along with five graph neural network architectures (GCN, GAT, MPNN, AttentiveFP, and FPGNN). The SVM::RDKitDes model performed best (AUC = 0.89, 1 = 0.78, BA = 0.80), with robustness confirmed by Y-scrambling and randomized-split analyses, and SHAP analysis identified 20 key descriptors of TDP1 inhibition. The model was deployed as a web application (http://drugpred.top:5050) and standalone desktop applications (.exe) are available at https://github.com/zenghuang8006/TDP1-inhibitor-prediction. The validated model was applied to screen 201 231 compounds, followed by drug-likeness filtering and hierarchical docking, yielding 16 candidates. Biological evaluation identified compound AO65 as a potent TDP1 inhibitor (IC = 0.80 ± 0.02 µM), and quantum chemical calculations and docking elucidated its electronic properties and binding within the catalytic domain. This work demonstrates the value of integrating ML-driven prediction with structure-based approaches and identifies AO65 as a promising lead for further TDP1-focused investigation. - Source: PubMed
Publication date: 2026/08/12
Zeng HuangZhang ManyiQiu BoZhang ShengyuanLiu JiayaoLuo XiaodongWu LingfengXie HuasongZhai MingYang JiunlongYang HaoNie HuaWang Nan - Herein, we report a solvent-controlled, operationally convenient and highly efficient rhodium(II)-catalysed protocol enabling hydrodehalogenation and phenanthridinone skeleton construction from 2-halobenzamide. This methodology facilitates the hydrodehalogenation of diverse 2-halobenzamides using isopropanol, providing quantitative yields without further purification. Furthermore, this strategy allows the direct and efficient conversion of 2‑halobenzamides into phenanthridinones by aprotic solvent. Additionally, a series of phenanthridinone derivatives were synthesised and evaluated for their inhibitory activities against tyrosyl-DNA phosphodiesterase 1 (TDP1) and topoisomerase IB (TOP1), as well as their cytotoxicity. Compound showed potent TDP1 inhibitory activity (IC = 4.5 ± 0.4 μM) and synergistic effect with topotecan and radiosensitising effect in HCT116 cells by stabilising cellular TDP1 cleavage complexes (TDP1cc). Compound exhibited strong TOP1 inhibition (+++) and induced the formation of cellular TOP1 cleavage complexes (TOP1cc) and DNA damage, and consequently triggered apoptosis. studies indicated that exhibits antitumor efficacy in HCT116 xenograft model. - Source: PubMed
Publication date: 2026/07/28
Hu De-XuanQin ChaoGao XiangTang LingZheng YaxinYin Rui - Tyrosyl-DNA phosphodiesterase 1 (TDP1) represents a compelling pharmacological target for the development of agents designed to circumvent tumor resistance to topoisomerase 1 (TOP1) inhibitors, a major class of clinically relevant antineoplastic drugs. This paper describes the design and synthesis of novel hybrid TDP1 inhibitors combining coumarin and monoterpene moieties via rigid isoxazole and 1,2,3-triazole heterocyclic linkers. The synthesis was accomplished via [3 + 2] cycloaddition of nitrile oxides to alkynes and copper-catalyzed click chemistry. Biological tests have demonstrated the crucial role of linker nature in the activity of the compounds. Isoxazole-linked conjugates showed strong inhibitory effects on TDP1, with IC values in the submicromolar to low micromolar range (0.8-3.2 μM). Overall, these values slightly surpassed those of the triazole-linked analogues, whose IC values ranged from 1.1 to 23.3 μM. At noncytotoxic doses, compounds and enhanced the sensitivity of human cervical cancer (HeLa) cells to the antitumor agent topotecan, a TOP1 inhibitor, thereby supporting the promise of this structural class as components of combination chemotherapy. - Source: PubMed
Publication date: 2026/07/19
Tsypyshev DmitriyKhomenko TatyanaKornienko TatyanaZakharenko AlexandraKomarova NinaKrasnov VyacheslavSoldatova NatalyaPostnikov PavelSari SuatVolcho KonstantinLavrik OlgaSalakhutdinov Nariman - [This corrects the article DOI: 10.17912/micropub.biology.000693.]. - Source: PubMed
Publication date: 2026/06/03
- The NF-κB signaling pathway is a key driver of inflammation and can be activated by many genotoxic stresses. Yet, the mechanisms by which different types of DNA damage trigger NF-κB remain poorly understood. In this study, we find that NF-κB activation by topoisomerase 1 (TOP1) inhibition is strongly increased when cells are treated in combination with PARP inhibitors. Mechanistically, we demonstrate that TOP1 inhibition activates ATM-mediated NF-κB signaling through two distinct pathways: a replication-dependent pathway triggered by replication fork collapse and a replication-independent pathway revealed upon PARP1 inhibition. We further show that PARP1 enzymatic activity is not required to suppress NF-κB signaling after TOP1 inhibition during the replication-independent pathway. Instead, PARP inhibitors trap PARP1 at DNA lesions, thereby blocking repair and promoting ATM-dependent NF-κB signaling, mimicking the cell response to TDP1 depletion. These findings reveal an unexpected role for PARP1 as an NF-κB activator when trapped at DNA lesions induced by TOP1 inhibition, providing a therapeutic opportunity to use PARP inhibitors to enhance inflammatory responses and potentially improve the efficacy of TOP1-targeted cancer therapies. - Source: PubMed
Bournique ElodieSanchez AmbrocioHa KimYan Katrina MManjunath LavanyaSantiago GisselleOrtega PedroBuisson Rémi