ArticleInvestigational new drugs2012
Borrelidin, a small molecule nitrile-containing macrolide inhibitor of threonyl-tRNA synthetase, is a potent inducer of apoptosis in acute lymphoblastic leukemia.
Article in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 60 citations in OpenAlex.
- Tuning tRNA synthetase inhibition reveals parabolic induction of stress granules limited in size and RNA content.RNA (New York, N.Y.) · 2026Article
- Borrelidin M: a new borrelidin derivative obtained from Streptomyces rochei VL-16 exhibited potent antibacterial and antiproliferative properties.International microbiology : the official journal of the Spanish Society for Microbiology · 2025Article
- Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from Actinomycetes.Antibiotics (Basel, Switzerland) · 2025Article
- Induction of proteasomal activity in mammalian cells by lifespan-extending tRNA synthetase inhibitors.GeroScience · 2024Article
- Multiomics ofInternational journal of molecular sciences · 2023Article
- Multiple Roles of the Stress Sensor GCN2 in Immune Cells.International journal of molecular sciences · 2023Review
- High-Throughput Screening Platform To Identify Inhibitors of Protein Synthesis with Potential for the Treatment of Malaria.Antimicrobial agents and chemotherapy · 2022Article
- Borrelidin from Saltern-Derived HalophilicJournal of Alzheimer's disease reports · 2021Article
- Aminoacyl-tRNA synthetases.RNA (New York, N.Y.) · 2020Review
- Targeting the unfolded protein response in head and neck and oral cavity cancers.Experimental cell research · 2019Review
- Cytochrome P450 Monooxygenase CYP139 Family Involved in the Synthesis of Secondary Metabolites in 824 Mycobacterial Species.International journal of molecular sciences · 2019Article
- Progress and challenges in aminoacyl-tRNA synthetase-based therapeutics.The Journal of biological chemistry · 2019Review
- Liposomal borrelidin for treatment of metastatic breast cancer.Drug delivery and translational research · 2018Article
- Alternative Splicing as a Target for Cancer Treatment.International journal of molecular sciences · 2018Review
- Potential therapeutic targets and small molecular drugs for pediatric B-precursor acute lymphoblastic leukemia treatment based on microarray data.Oncology letters · 2017Article
- Borrelidin Induces the Unfolded Protein Response in Oral Cancer Cells and Chop-Dependent Apoptosis.ACS medicinal chemistry letters · 2015Article
- Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor.Scientific reports · 2015Article
- Structural basis for full-spectrum inhibition of translational functions on a tRNA synthetase.Nature communications · 2015Article
- Extracellular matrix as target for antitumor therapy.OncoTargets and therapy · 2015Review
- Genetic validation of aminoacyl-tRNA synthetases as drug targets in Trypanosoma brucei.Eukaryotic cell · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Due to the poor prognosis and limited therapeutic options for adult patients with acute lymphoblastic leukemia (ALL), development of novel therapies is much needed to prolong patient survival and increase the efficacy of their treatment. Malignant T cells need high levels of nutrients to maintain their proliferation rate. Borrelidin, a small molecule nitrile-containing macrolide, is an inhibitor of bacterial and eukaryal threonyl-tRNA synthetase. Borrelidin-mediated inhibition of aminoacyl-tRNA synthesis, leads to an induction in the levels of uncharged tRNA, nutritional stress and ultimately inhibition of protein synthesis. The aim of the present study was to investigate whether borrelidin treatment inhibits the proliferation of malignant ALL cell lines, Jurkat and CEM cells, and study the mechanism by which this drug acts. Our results show that borrelidin was able to potently inhibit the proliferation of ALL cell lines with a half maximal inhibitory concentration of 50 ng/ml. Borrelidin showed a greater inhibitory effect on ALL cell lines compared to primary fibroblasts. Flow cytometry and western blot analysis indicated that borrelidin was able to increase the level of apoptosis and cause G(1) arrest in ALL cell lines. Activation of the general control nonderepressible-2 (GCN2) kinase stress responsive pathway and induction of CHOP protein was significantly higher in ALL cell lines treated with borrelidin. These findings collectively suggest for the first time that borrelidin targets ALL cell lines by inducing apoptosis and mediating G(1) arrest and that borrelidin treatment in ALL cell lines is correlated with activation of the GCN2 kinase pathway.
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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.