ArticleACS medicinal chemistry letters2019
Identification of Novel, Potent, and Orally Available GCN2 Inhibitors with Type I Half Binding Mode.
Article in ACS medicinal chemistry letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 39 citations in OpenAlex.
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- GCN2 in proteostasis: structural logic, signalling networks and disease.The FEBS journal · 2026Review
- Structural Transformation of a BRAF Inhibitor into a Selective PKR Inhibitor.Journal of medicinal chemistry · 2026Article
- An inhibitor of GCN2 and the integrated stress response directly targets ZAK protein kinase to limit cytotoxicity.The Journal of biological chemistry · 2026Article
- GCN2 in Cancer: Molecular Mechanisms to Therapeutic Potential.Current cancer drug targets · 2026Review
- RAF inhibitors activate the integrated stress response by direct activation of GCN2.Nature communications · 2025Article
- Isolation of New Chemical Modulators of the Interaction Between HIV-1 Integrase and the Cellular Restriction Factor GCN2.Viruses · 2025Article
- Structural insights into allosteric inhibition of HRI kinase by heme binding via HDX-MS.The Biochemical journal · 2025Article
- Structure of a Gcn2 dimer in complex with the large 60S ribosomal subunit.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cryo-EM structure of histidyl-tRNA synthetase-like domain reveals activating crossed helices at the core of GCN2.PNAS nexus · 2024Article
- Multifaceted role of GCN2 in tumor adaptation and therapeutic targeting.Translational oncology · 2024Review
- Activation of the integrated stress response by inhibitors of its kinases.Nature communications · 2023Article
- Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).Cancer cell international · 2023Review
- The amino-acid stress sensing eIF2α kinase GCN2 is a survival biomarker for malignant mesothelioma.BJC reports · 2023Article
- GCN2 inhibition sensitizes arginine-deprived hepatocellular carcinoma cells to senolytic treatment.Cell metabolism · 2022Article
- Novel Insights on the Use of L-Asparaginase as an Efficient and Safe Anti-Cancer Therapy.Cancers · 2022Review
- Translational Activation of ATF4 through Mitochondrial Anaplerotic Metabolic Pathways Is Required for DLBCL Growth and Survival.Blood cancer discovery · 2022Article
- Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence.Nature communications · 2021Article
- The integrated stress response in pulmonary disease.European respiratory review : an official journal of the European Respiratory Society · 2020Review
- Targeting Protein Synthesis in Colorectal Cancer.Cancers · 2020Review
Corrections and comments
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Authors and funding
26 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
General control nonderepressible 2 (GCN2) is a master regulator kinase of amino acid homeostasis and important for cancer survival in the tumor microenvironment under amino acid depletion. We initiated studies aiming at the discovery of novel GCN2 inhibitors as first-in-class antitumor agents and conducted modification of the substructure of sulfonamide derivatives with expected type I half binding on GCN2. Our synthetic strategy mainly corresponding to the αC-helix allosteric pocket of GCN2 led to significant enhancement in potency and a good pharmacokinetic profile in mice. In addition, compound
Identifiers
What OpenQuestion holds
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.