ArticleAutophagy2023
Multiparameter phenotypic screening for endogenous TFEB and TFE3 translocation identifies novel chemical series modulating lysosome function.
Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy.Molecules (Basel, Switzerland) · 2026Review
- Targeting chaperone-mediated autophagy to regulate osteoclast activity as a therapeutic strategy for osteoporosis.Materials today. Bio · 2025Article
- Article
- Impairment of lysosomal quality control in Huntington disease.Cell death & disease · 2025Article
- Chronic Exercise Protects Against Cognitive Deficits in an Alzheimer's Disease Model by Enhancing Autophagy and Reducing Mitochondrial Abnormalities.Molecular neurobiology · 2025Article
- Lysosomes in the immunometabolic reprogramming of immune cells in atherosclerosis.Nature reviews. Cardiology · 2025Review
- High throughput screening assay for the identification of ATF4 and TFEB activating compounds.Autophagy reports · 2025Article
- Lysosomal CaScientific reports · 2024Article
- CRISPRi: a way to integrate iPSC-derived neuronal models.Biochemical Society transactions · 2024Review
- Protein kinase D1 - A targetable mediator of pancreatic cancer development.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons.Molecular neurodegeneration · 2023Article
- Gemcitabine promotes autophagy and lysosomal function through ERK- and TFEB-dependent mechanisms.Cell death discovery · 2023Article
- Small Molecule Inhibitors of Protein Kinase D: Early Development, Current Approaches, and Future Directions.Journal of medicinal chemistry · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The accumulation of toxic protein aggregates in multiple neurodegenerative diseases is associated with defects in the macroautophagy/autophagy-lysosome pathway. The amelioration of disease phenotypes across multiple models of neurodegeneration can be achieved through modulating the master regulator of lysosome function, TFEB (transcription factor EB). Using a novel multi-parameter high-throughput screen for cytoplasmic:nuclear translocation of endogenous TFEB and the related transcription factor TFE3, we screened the Published Kinase Inhibitor Set 2 (PKIS2) library as proof of principle and to identify kinase regulators of TFEB and TFE3. Given that TFEB and TFE3 are responsive to cellular stress we have established assays for cellular toxicity and lysosomal function, critical to ensuring the identification of hit compounds with only positive effects on lysosome activity. In addition to AKT inhibitors which regulate TFEB localization, we identified a series of quinazoline-derivative compounds that induced TFEB and TFE3 translocation. A novel series of structurally-related analogs was developed, and several compounds induced TFEB and TFE3 translocation at higher potency than previously screened compounds. KINOME
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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.