ArticleThe Journal of biological chemistry2016
Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 87 citations in OpenAlex.
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- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- RNA modifications in health and disease: from mechanistic insights to therapeutic applications.Precision clinical medicine · 2025Review
- SlALKBH9B is involved in drought-induced flower drop by regulating ethylene production.Horticulture research · 2025Article
- Repurposing FDA-approved drugs to find a novel inhibitor of alpha-ketoglutarate-dependent dioxygenase FTO to treat esophageal cancer.Research in pharmaceutical sciences · 2025Article
- Phytochemical Analysis and Biological Activities of Flavonoids and Anthraquinones fromPlants (Basel, Switzerland) · 2025Article
- The role and clinical potential of RNA modifications in bladder cancer.Bladder (San Francisco, Calif.) · 2025Review
- Targeting DTX2/UFD1-mediated FTO degradation to regulate antitumor immunity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Role of N6-methyladenosine Modification in Gametogenesis and Embryogenesis: Impact on Fertility.Genomics, proteomics & bioinformatics · 2024Review
- Clinician's Guide to Epitranscriptomics: An Example of NLife (Basel, Switzerland) · 2024Review
- Methylation modifications in tRNA and associated disorders: Current research and potential therapeutic targets.Cell proliferation · 2024Review
- A covalent compound selectively inhibits RNA demethylase ALKBH5 rather than FTO.RSC chemical biology · 2024Article
- NJournal of translational internal medicine · 2024Article
- Current insights on m6A RNA modification in acute leukemia: therapeutic targets and future prospects.Frontiers in oncology · 2024Review
- A new wave of innovations within the DNA damage response.Signal transduction and targeted therapy · 2023Review
- N6-methyladenosine RNA methylation in liver diseases: from mechanism to treatment.Journal of gastroenterology · 2023Review
- Recent advances in the discovery of plant-derived antimicrobial natural products to combat antimicrobial resistant pathogens: insights from 2018-2022.Natural product reports · 2023Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The AlkB repair enzymes, including Escherichia coli AlkB and two human homologues, ALKBH2 and ALKBH3, are iron(II)- and 2-oxoglutarate-dependent dioxygenases that efficiently repair N(1)-methyladenine and N(3)-methylcytosine methylated DNA damages. The development of small molecule inhibitors of these enzymes has seen less success. Here we have characterized a previously discovered natural product rhein and tested its ability to inhibit AlkB repair enzymes in vitro and to sensitize cells to methyl methane sulfonate that mainly produces N(1)-methyladenine and N(3)-methylcytosine lesions. Our investigation of the mechanism of rhein inhibition reveals that rhein binds to AlkB repair enzymes in vitro and promotes thermal stability in vivo In addition, we have determined a new structural complex of rhein bound to AlkB, which shows that rhein binds to a different part of the active site in AlkB than it binds to in fat mass and obesity-associated protein (FTO). With the support of these observations, we put forth the hypothesis that AlkB repair enzymes would be effective pharmacological targets for cancer treatment.
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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.