ArticleEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences2021
Identification of harmine and β-carboline analogs from a high-throughput screen of an approved drug collection; profiling as differential inhibitors of DYRK1A and monoamine oxidase A and for in vitro and in vivo anti-cancer studies.
Article in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Harmaline and the gut-brain-immune axis: a novel therapeutic avenue in neuroinflammation and ulcerative colitis.Inflammopharmacology · 2026Review
- Integrative Insights Into DYRK1A From Molecular Function to Therapeutic Advancement.Chemical biology & drug design · 2026Review
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Network pharmacology analysis and experimental validation of the gastric cancer-related targets of harmine.Scientific reports · 2026Article
- Harmine Derivatives as Anticancer Agents Endowed With Potent and Selective Antileukemia Activity: Synthesis, Biological Evaluation, Proapoptotic and Genotoxic Activity.Archiv der Pharmazie · 2026Article
- Harmine hydrochloride induces G0/G1 cell cycle arrest and apoptosis in oral squamous carcinoma cells.Experimental and therapeutic medicine · 2025Article
- Towards Imaging Tau Hyperphosphorylation: Is DYRK1A a Potential Target for Imaging Hyperphosphorylation of Tau? Molecular Modeling Assessment and Synthesis of [Molecules (Basel, Switzerland) · 2025Article
- Exploration of the potential neurotransmitter or neuromodulator-like properties of harmine: evidence from synthesis to synaptic modulation.Frontiers in pharmacology · 2025Article
- Beyond CTLA-4 and PD-1: Novel Insights into MAO-A as a Next Generation Immune Checkpoint Modulator for Cancer Immunotherapy.Current cancer drug targets · 2025Review
- Identification of mitochondrial ATP synthase as the cellular target of Ru-polypyridyl-National science review · 2024Article
- Identification of Novel GANT61 Analogs with Activity in Hedgehog Functional Assays and GLI1-Dependent Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Article
- Harmol used for the treatment of herpes simplex virus induced keratitis.Virology journal · 2024Article
- Formation, Identification, and Occurrence of the Furan-Containing β-Carboline Flazin Derived from l-Tryptophan and Carbohydrates.Journal of agricultural and food chemistry · 2024Article
- Head-to-head comparison of [Acta neuropathologica · 2024Article
- Identification, Formation, and Occurrence of Perlolyrine: A β-Carboline Alkaloid with a Furan Moiety in Foods.Journal of agricultural and food chemistry · 2023Article
- Anti-Diabetic and Anti-Adipogenic Effect of Harmine in High-Fat-Diet-Induced Diabetes in Mice.Life (Basel, Switzerland) · 2023Article
- Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models.Nature communications · 2023Article
- β-Carboline Alkaloids in Soy Sauce and Inhibition of Monoamine Oxidase (MAO).Molecules (Basel, Switzerland) · 2023Article
- Regeneration of Pancreatic β-Cells for Diabetes Therapeutics by Natural DYRK1A Inhibitors.Metabolites · 2022Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1a) is highly expressed in glioma, an aggressive brain tumor, and has been proposed as a therapeutic target for cancer. In the current study, we have used an optimized and validated time-resolved fluorescence energy transfer (TR-FRET)-based DYRK1A assay for high-throughput screening (HTS) in 384-well format. A small-scale screen of the FDA-approved Prestwick drug collection identified the β-carboline, harmine, and four related analogs as DYRK1A inhibitors. Hits were confirmed by dose response and in an orthogonal DYRK1A assay. Harmine's potential therapeutic use has been hampered by its off-target activity for monoamine oxidase A (MAO-A) which impacts multiple nervous system targets. Selectivity profiling of harmine and a broader collection of analogs allowed us to map some divergent SAR (structure-activity relationships) for the DYRK1A and MAO-A activities. The panel of harmine analogs had varying activities in vitro in glioblastoma (GBM) cell lines when tested for anti-proliferative effects using a high content imaging assay. In particular, of the identified analogs, harmol was found to have the best selectivity for DYRK1A over MAO-A and, when tested in a glioma tumor xenograft model, harmol demonstrated a better therapeutic window compared to harmine.
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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.