ArticleGenes & cancer2013
Phenothiazine Inhibitors of TLKs Affect Double-Strand Break Repair and DNA Damage Response Recovery and Potentiate Tumor Killing with Radiomimetic Therapy.
Article in Genes & cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Knockdown of Tousled‑like kinase 1 inhibits survival of glioblastoma multiforme cells.International journal of molecular medicine · 2020Pooled it
- The Interaction of Structural Analogues of Phenothiazines in p53-Dependent Cellular Signaling Pathways.ACS omega · 2026Article
- Targeting TLK2 with antisense oligonucleotides as a new strategy in acute myeloid leukemia.Frontiers in oncology · 2026Article
- Chromatin looping-based CRISPR screen identifies TLK2 as chromatin loop formation regulator in cancer stemness plasticity.Nature communications · 2025Article
- TLK1 as a therapeutic target in TMZ resistant glioblastoma using small molecule inhibitor.Scientific reports · 2025Article
- A TLK2-mediated calcium-driven cell death pathway links neuronal degeneration to nuclear envelope disruption.Nature communications · 2025Article
- Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.Nucleic acids research · 2025Article
- Tousled-like kinase loss confers PARP inhibitor resistance in BRCA1-mutated cancers by impeding non-homologous end joining repair.Molecular medicine (Cambridge, Mass.) · 2025Article
- Beyond the Horizon: Rethinking Prostate Cancer Treatment Through Innovation and Alternative Strategies.Cancers · 2024Article
- Discovery and optimization of narrow spectrum inhibitors of Tousled like kinase 2 (TLK2) using quantitative structure activity relationships.European journal of medicinal chemistry · 2024Article
- Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.bioRxiv : the preprint server for biology · 2024Article
- Discovery and Optimization of Narrow Spectrum Inhibitors of Tousled Like Kinase 2 (TLK2) Using Quantitative Structure Activity Relationships.bioRxiv : the preprint server for biology · 2023Article
- Exploiting TLK1 and Cisplatin Synergy for Synthetic Lethality in Androgen-Insensitive Prostate Cancer.Biomedicines · 2023Article
- TLK1-mediated RAD54 phosphorylation spatio-temporally regulates Homologous Recombination Repair.Nucleic acids research · 2023Article
- Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair.International journal of molecular sciences · 2023Review
- Targeting Prostate Cancer, the 'Tousled Way'.International journal of molecular sciences · 2023Review
- Tousled-like kinase 1: a novel factor with multifaceted role in mCRPC progression and development of therapy resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Targeting protein phosphatase PP2A for cancer therapy: development of allosteric pharmaceutical agents.Clinical science (London, England : 1979) · 2021Review
- Article
- ERα-related chromothripsis enhances concordant gene transcription on chromosome 17q11.1-q24.1 in luminal breast cancer.BMC medical genomics · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Tousled-like kinases (TLKs) are involved in chromatin assembly, DNA repair, and transcription. Two TLK genes exist in humans, and their expression is often dysregulated in cancer. TLKs phosphorylate Asf1 and Rad9, regulating double-strand break (DSB) repair and the DNA damage response (DDR). TLKs maintain genomic stability and are important therapeutic intervention targets. We identified specific inhibitors of TLKs from several compound libraries, some of which belong to the family of phenothiazine antipsychotics. The inhibitors prevented the TLK-mediated phosphorylation of Rad9(S328) and impaired checkpoint recovery and DSB repair. The inhibitor thioridazine (THD) potentiated tumor killing with chemotherapy and also had activity alone. Staining for γ-H2AX revealed few positive cells in untreated tumors, but large numbers in mice treated with low doxorubicin or THD alone, possibly the result of the accumulation of DSBs that are not promptly repaired as they may occur in the harsh tumor growth environment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.