ArticleChemical science2019
Label-free target identification reveals oxidative DNA damage as the mechanism of a selective cytotoxic agent.
Article in Chemical science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Label-Free Target Discovery Strategy for Natural Active Products.Biomolecules · 2026Review
- MTH1 in the disorders of the central nervous system: scope beyond brain tumors and challenges.Acta neurologica Belgica · 2025Review
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- Inflachromene ameliorates Parkinson's disease by targeting Nrf2-binding Keap1.Chemical science · 2024Article
- Targeting the nucleic acid oxidative damage repair enzyme MTH1: a promising therapeutic option.Frontiers in cell and developmental biology · 2024Review
- The Role of Protein Arginine Methyltransferases in DNA Damage Response.International journal of molecular sciences · 2022Review
- An update of label-free protein target identification methods for natural active products.Theranostics · 2022Review
- Callyspongiolide kills cells by inducing mitochondrial dysfunction via cellular iron depletion.Communications biology · 2021Article
- Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives.Acta pharmaceutica Sinica. B · 2020Review
- AXL and CAV-1 play a role for MTH1 inhibitor TH1579 sensitivity in cutaneous malignant melanoma.Cell death and differentiation · 2020Article
- Construction of a self-directed replication system for label-free and real-time sensing of repair glycosylases with zero background.Chemical science · 2020Article
- Karonudib is a promising anticancer therapy in hepatocellular carcinoma.Therapeutic advances in medical oncology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phenotypic screening can not only identify promising first-in-class drug candidates, but can also reveal potential therapeutic targets or neomorphic functions of known proteins. In this study, we identified target proteins of SB2001, a cytotoxic agent that acts specifically against HeLa human cervical cancer cells. Because SB2001 lacks chemical modification sites, label-free target identification methods including thermal stability shift-based fluorescence difference in two-dimensional gel electrophoresis (TS-FITGE) and thermal proteome profiling (TPP) were applied to characterize its mechanism of action. Owing to their differences, the two label-free target identification methods uncovered complementary target candidates. Candidates from both methods were prioritized according to their selective lethality upon the knockdown of those genes in HeLa cells, compared to CaSki cells which were used as a negative control cell line from the human cervix. LTA4H was identified only by TS-FITGE, but not by TPP, because only one isoform was stabilized by SB2001. Furthermore, it was implied that a non-canonical function of LTA4H was involved in the SB2001 activity. MTH1 was identified by both TS-FITGE and TPP, and SB2001 inhibited the function of MTH1 in hydrolyzing oxidized nucleotides. Compared to CaSki cells, HeLa cells displayed downregulated DNA mismatch repair pathways, which made HeLa cells more susceptible to the oxidative stress caused by SB2001, resulting in increased 8-oxoG concentrations, DNA damage, and subsequent cell death.
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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.