ArticleProceedings of the National Academy of Sciences of the United States of America2023
A small-molecule drug inhibits autophagy gene expression through the central regulator TFEB.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 54 citations in OpenAlex.
- Autophagy inhibition sensitizes radiotherapy responses in high-grade mutant IDH1 glioma.Nature communications · 2026Article
- Exploring the Neuroprotective Effects of Walnut (International journal of molecular sciences · 2026Article
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- SASP-driven vascular aging: unraveling the transcriptional nexus in endothelial senescence and cardiovascular disease.Histochemistry and cell biology · 2026Review
- Naringenin ameliorates swine pulpitis by modulating immune response.BMC oral health · 2026Article
- Endosome traffic in rheumatic diseases: mechanistic insights and therapeutic opportunities.Nature reviews. Rheumatology · 2026Review
- Identification of non-oncology drugs with activity against inflammatory and triple-negative breast cancer cell lines.Oncology letters · 2026Article
- tRNA mMolecular cancer · 2026Article
- Helminth Infection, Gut Microbiome Alterations, and Their Impact on Pulmonary Tuberculosis Susceptibility.Journal of tropical medicine · 2026Review
- A Novel Autophagy InhibitorResearch (Washington, D.C.) · 2026Article
- Editorial: Unlocking autophagy's full potential: embracing a multidimensional approach for targeted cancer treatment.Frontiers in pharmacology · 2026Article
- Limited therapeutic efficacy of N-acetyl-L-leucine in a mouse model of CLN1 disease.Scientific reports · 2025Article
- Apoptotic extracellular vesicles from peripancreatic adipose-derived mesenchymal stem cells ameliorate severe acute pancreatitis through the transcription factor EB-mediated autophagy-lysosomal pathway: an experimental study.International journal of surgery (London, England) · 2025Article
- Ubiquitination of TFEB increased intestinal permeability to aggravate metabolic dysfunction-associated steatohepatitis.Hepatology (Baltimore, Md.) · 2025Article
- Transaldolase 1 impacts Parkinson's disease pathogenesis via metabolic reprogramming and autophagy-lysosomal pathway.Acta neuropathologica communications · 2025Article
- TRIM28 drives immune evasion via PARP1 SUMOylation and NADJournal for immunotherapy of cancer · 2025Article
- Transcriptional Dysregulation of Autophagy in Aging and Potential Interventions: Insights Into TFEB and FOXOs.Frontiers in bioscience (Landmark edition) · 2025Review
- TFE3-rearranged and TFEB-altered renal cell carcinoma: from classification to real-life. Insights from a national Italian survey.Pathologica · 2025Article
- Folliculin Deletion in the Mouse Kidney Results in Cystogenesis of the Loops of Henle via Aberrant TFEB Activation.The American journal of pathology · 2025Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy supports the fast growth of established tumors and promotes tumor resistance to multiple treatments. Inhibition of autophagy is a promising strategy for tumor therapy. However, effective autophagy inhibitors suitable for clinical use are currently lacking. There is a high demand for identifying novel autophagy drug targets and potent inhibitors with drug-like properties. The transcription factor EB (TFEB) is the central transcriptional regulator of autophagy, which promotes lysosomal biogenesis and functions and systematically up-regulates autophagy. Despite extensive evidence that TFEB is a promising target for autophagy inhibition, no small molecular TFEB inhibitors were reported. Here, we show that an United States Food and Drug Administration (FDA)-approved drug Eltrombopag (EO) binds to the basic helix-loop-helix-leucine zipper domain of TFEB, specifically the bottom surface of helix-loop-helix to clash with DNA recognition, and disrupts TFEB-DNA interaction in vitro and in cellular context. EO selectively inhibits TFEB's transcriptional activity at the genomic scale according to RNA sequencing analyses, blocks autophagy in a dose-dependent manner, and increases the sensitivity of glioblastoma to temozolomide in vivo. Together, this work reveals that TFEB is targetable and presents the first direct TFEB inhibitor EO, a drug compound with great potential to benefit a wide range of cancer therapies by inhibiting autophagy.
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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.