ArticlePloS one2016
Discovery of a Novel, Isothiazolonaphthoquinone-Based Small Molecule Activator of FOXO Nuclear-Cytoplasmic Shuttling.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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
18 citing papers in PubMed, 33 citations in OpenAlex.
- Research progress on the mechanism of FOXO protein in sepsis.Apoptosis : an international journal on programmed cell death · 2026Review
- Molecular Hybridization of Naphthoquinones and Thiazoles: A Promising Strategy for Anticancer Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Dysfunction of Autophagy in Adipose Tissue Macrophages Regulated via FoxO1 in Obesity-Related Severe Acute Pancreatitis.International journal of molecular sciences · 2025Article
- Article
- FoxO1 promotes ovarian cancer by increasing transcription and METTL14-mediated mCancer science · 2024Article
- Enhanced anticancer synergy of LOM612 in combination with selinexor: FOXO1 nuclear translocation-mediated inhibition of Wnt/β-catenin signaling pathway in breast cancer.Cancer chemotherapy and pharmacology · 2024Article
- MicroRNAs as the Critical Regulators of Forkhead Box Protein Family in Pancreatic, Thyroid, and Liver Cancers.Biochemical genetics · 2023Review
- Mitochondrial carrier 1 (MTCH1) governs ferroptosis by triggering the FoxO1-GPX4 axis-mediated retrograde signaling in cervical cancer cells.Cell death & disease · 2023Article
- Synthesis and biological activity evaluation of 3-(hetero) arylideneindolin-2-ones as potential c-Src inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Target identification for small-molecule discovery in the FOXO3a tumor-suppressor pathway using a biodiverse peptide library.Cell chemical biology · 2021Article
- Review
- Oxidative Stress-Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives.Oxidative medicine and cellular longevity · 2021Review
- Therapeutic strategies targeting FOXO transcription factors.Nature reviews. Drug discovery · 2021Review
- Genetics of extreme human longevity to guide drug discovery for healthy ageing.Nature metabolism · 2020Review
- Nuclear-cytoplasmic Shuttling in Chronic Myeloid Leukemia: Implications in Leukemia Maintenance and Therapy.Cells · 2019Review
- The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells.Scientific reports · 2019Article
- The Dominant Role of Forkhead Box Proteins in Cancer.International journal of molecular sciences · 2018Review
- FOXO3 and Exceptional Longevity: Insights From Hydra to Humans.Current topics in developmental biology · 2018Article
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 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FOXO factors are tumour suppressor proteins commonly inactivated in human tumours by posttranslational modifications. Furthermore, genetic variation within the FOXO3a gene is consistently associated with human longevity. Therefore, the pharmacological activation of FOXO proteins is considered as an attractive therapeutic approach to treat cancer and age-related diseases. In order to identify agents capable of activating FOXOs, we tested a collection of small chemical compounds using image-based high content screening technology. Here, we report the discovery of LOM612 (compound 1a), a newly synthesized isothiazolonaphthoquinone as a potent FOXO relocator. Compound 1a induces nuclear translocation of a FOXO3a reporter protein as well as endogenous FOXO3a and FOXO1 in U2OS cells in a dose-dependent manner. This activity does not affect the subcellular localization of other cellular proteins including NFkB or inhibit CRM1-mediated nuclear export. Furthermore, compound 1a shows a potent antiproliferative effect in human cancer cell lines.
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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.