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
- Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a potential radiotherapeutic target for cancer treatment. Herein, two series of analogues, benzophenanthridinone derivatives and benzophenanthridine derivatives, were designed and synthesized based on the reported TDP1 inhibitor NTD119B showing strong radiosensitization in vitro and in vivo. The structural modification gave seventeen analogues with stronger TDP1 inhibitory activity than NTD119B (IC = 6.9 μM). B11 showed the most potent TDP1 inhibition (IC = 1.2 ± 0.7 μM), 5.8-fold greater than NTD119B. Colony formation assays showed four TDP1 inhibitors A6, A26, B1, B7 showing stronger radiosensitizing activity than NTD119B in HCT116 cells. Further studies demonstrate that A6 targets TDP1 in cells and suppresses NHEJ repair activity, enhancing ionizing radiation-induced DNA damage resulting in a strong radiosensitizing activity both in HCT116 cells and xenografts animal model. The structure-activity relationship for TDP1 inhibition is also analyzed. - Source: PubMed
Publication date: 2026/04/27
Hu De-XuanLi Yue-WenChen AoQin ChaoZhang Jian-QiangLiang Zi-QiongAgama KeliPommier YvesWang HuaimingAn Lin-Kun - Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a key enzyme for the repair of stalled topoi-somerase 1 (TOP1)-DNA complexes. We have previously developed a TDP1 inhibitor, compound OL9-116, which is capable of enhancing the action of the anticancer drug topotecan (TPC), a TOP1 poison, in vitro and in vivo. In this study, the inhibition mode of OL9-116 (uncompetitive) was investigated. We have shown that N-terminal domain of TDP1, which is important for the cell function of TDP1 but is not involved in catalysis directly, reduced the inhibitory potency of OL9-116 probably by influencing the conformation of the enzyme. OL9-116 did not reduce cell viability and did not affect mitochondrial membrane potential. OL9-116 enhanced the cytotoxic/antiproliferative effect of TPC on the panel of tumor cells. This effect was not observed on nontumor cells or TDP1-deficient cells. OL9-116 and TPC had different effects on and gene expression detected by PCR depending on the cell type and the presence of functional TDP1. The direct relation between the effects of the compounds on the gene expression and cell survival was not found. The obtained data indicated a synergistic effect of OL9-116 and TPC, which appeared to be mediated by TDP1 inhibition rather than by an effect on gene expression. - Source: PubMed
Publication date: 2026/04/21
Kornienko Tatyana EChepanova Arina AKolobenko Maria VChernyshova Irina AZakharenko Alexandra LVenzel Artur SDyrkheeva Nadezhda SMarkov Andrey VAnarbaev Rashid ONaumenko Konstantin NLuzina Olga ASalakhutdinov Nariman FIvanisenko Vladimir ALavrik Olga I - 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