ArticleMolecular cell2015
Small Molecule Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates.
Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 461 papers.
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Who cites it
461 citing papers in PubMed, 710 citations in OpenAlex.
- Lysosomal metabolism in pancreatic cancer and its crosstalk with host physiology.Genes & development · 2026Review
- Drugging small-molecule compounds in autophagy-dependent cell death to overcome cancer therapy resistance.Apoptosis : an international journal on programmed cell death · 2026Review
- Reconstitution of multistep recruitment of ULK1 to membranes in autophagy.Science advances · 2026Article
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Reprogramming Autophagy to Strengthen Antitumour Immunity: Advances in Immunotherapeutic Strategies.Immunology · 2026Review
- AMPK Therapy-A Little Goes A Long Way.Cells · 2026Review
- The Role of Autophagy in Cancer Evolution and Prognosis, Highlighting Its Role in PCa and Its Interaction with Apoptosis and Epigenetic Regulation by miRNAs.Medical sciences (Basel, Switzerland) · 2026Review
- Autophagy Modulation in Cancer Therapy: Navigating the Dual Roles to Overcome Chemoresistance.Health science reports · 2026Article
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- VPS33A Promotes Pemigatinib Resistance in Cholangiocarcinoma via Autophagy.Digestive diseases and sciences · 2026Article
- Regulatory mechanisms of post-translational modifications on autophagic flux in neurons following ischemic stroke.Molecular biology reports · 2026Review
- Protocol to study direct (de)phosphorylation events on a proteome-wide scale using on-bead in vitro enzyme assays.STAR protocols · 2026Article
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- The ULK1-NCOA3 axis restrains de novo lipogenesis and prevents diet-induced steatohepatitis and fibrosis in mice.The Journal of clinical investigation · 2026Article
- A ULK1-MTFR1L feedback loop links mitochondrial fission, mitophagy and apoptosis.Journal of cell science · 2026Article
- Targeting Autophagy to Overcome Chemoresistance and Immune Resistance in Triple-Negative Breast Cancer.Cancers · 2026Review
- Oxidative stress induced by DMSA-IONPs impairs breast cancer cell migration and paracrine cell communication.Journal of nanobiotechnology · 2026Article
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Autophagy Modulation in Cancer Immunotherapy, Emerging Molecular Targets and Drug Selection Strategies.International journal of molecular sciences · 2026Review
- Autophagy in Cancer: Context-Dependent Regulation and Precision Nanomedicine-Enabled Therapeutic Targeting.Biomedicines · 2026Review
401 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Many tumors become addicted to autophagy for survival, suggesting inhibition of autophagy as a potential broadly applicable cancer therapy. ULK1/Atg1 is the only serine/threonine kinase in the core autophagy pathway and thus represents an excellent drug target. Despite recent advances in the understanding of ULK1 activation by nutrient deprivation, how ULK1 promotes autophagy remains poorly understood. Here, we screened degenerate peptide libraries to deduce the optimal ULK1 substrate motif and discovered 15 phosphorylation sites in core autophagy proteins that were verified as in vivo ULK1 targets. We utilized these ULK1 substrates to perform a cell-based screen to identify and characterize a potent ULK1 small molecule inhibitor. The compound SBI-0206965 is a highly selective ULK1 kinase inhibitor in vitro and suppressed ULK1-mediated phosphorylation events in cells, regulating autophagy and cell survival. SBI-0206965 greatly synergized with mechanistic target of rapamycin (mTOR) inhibitors to kill tumor cells, providing a strong rationale for their combined use in the clinic.
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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.