ArticlePloS one2015
Selectivity Profiling and Biological Activity of Novel β-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03624556 (Pediatric Exploratory Research Study of EGCG Use and Safety), which is not on this map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Pediatric Exploratory Research Study of EGCG Use and Safety (PERSEUS)
Who cites it
24 citing papers in PubMed, 62 citations in OpenAlex.
- 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
- The protein kinase DYRK1B is a p53 target gene and functions as a negative feedback regulator of the transcription factor RFX7.Cell death & disease · 2026Article
- Discovery of indole- and quinolone-based inhibitors of the mTOR/Akt/Pi3K pathway for the potential treatment of autism and certain types of cancer.RSC medicinal chemistry · 2026Article
- Functional characterization of two DYRK1B variants causative of AOMS3.Orphanet journal of rare diseases · 2024Article
- Article
- Psychoplastogenic DYRK1A Inhibitors with Therapeutic Effects Relevant to Alzheimer's Disease.Journal of medicinal chemistry · 2024Article
- Synthesis and Kinase Inhibitory Potencies of Pyrazolo[3,4-Molecules (Basel, Switzerland) · 2022Article
- The chromosome 21 kinase DYRK1A: emerging roles in cancer biology and potential as a therapeutic target.Oncogene · 2022Review
- DYRK1A suppression attenuates HIF‑1α accumulation and enhances the anti‑liver cancer effects of regorafenib and sorafenib under hypoxic conditions.International journal of oncology · 2022Article
- Rational Design and Identification of Harmine-Inspired, N-Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic In Vivo Drosophila Model System.ChemMedChem · 2022Article
- Review
- GSK-3β, FYN, and DYRK1A: Master Regulators in Neurodegenerative Pathways.International journal of molecular sciences · 2021Review
- 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.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2021Article
- The stress-responsive kinase DYRK2 activates heat shock factor 1 promoting resistance to proteotoxic stress.Cell death and differentiation · 2021Article
- How to Separate Kinase Inhibition from Undesired Monoamine Oxidase A Inhibition-The Development of the DYRK1A Inhibitor AnnH75 from the Alkaloid Harmine.Molecules (Basel, Switzerland) · 2020Article
- Compounds from Natural Sources as Protein Kinase Inhibitors.Biomolecules · 2020Review
- A 3D culture platform enables development of zinc-binding prodrugs for targeted proliferation of β cells.Science advances · 2020Article
- The nuclear interactome of DYRK1A reveals a functional role in DNA damage repair.Scientific reports · 2019Article
- How to design potent and selective DYRK1B inhibitors? Molecular modeling study.Journal of molecular modeling · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DYRK1A is a pleiotropic protein kinase with diverse functions in cellular regulation, including cell cycle control, neuronal differentiation, and synaptic transmission. Enhanced activity and overexpression of DYRK1A have been linked to altered brain development and function in Down syndrome and neurodegenerative diseases such as Alzheimer's disease. The β-carboline alkaloid harmine is a high affinity inhibitor of DYRK1A but suffers from the drawback of inhibiting monoamine oxidase A (MAO-A) with even higher potency. Here we characterized a series of novel harmine analogs with minimal or absent MAO-A inhibitory activity. We identified several inhibitors with submicromolar potencies for DYRK1A and selectivity for DYRK1A and DYRK1B over the related kinases DYRK2 and HIPK2. An optimized inhibitor, AnnH75, inhibited CLK1, CLK4, and haspin/GSG2 as the only off-targets in a panel of 300 protein kinases. In cellular assays, AnnH75 dose-dependently reduced the phosphorylation of three known DYRK1A substrates (SF3B1, SEPT4, and tau) without negative effects on cell viability. AnnH75 inhibited the cotranslational tyrosine autophosphorylation of DYRK1A and threonine phosphorylation of an exogenous substrate protein with similar potency. In conclusion, we have characterized an optimized β-carboline inhibitor as a highly selective chemical probe that complies with desirable properties of drug-like molecules and is suitable to interrogate the function of DYRK1A in biological studies.
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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.