ArticleDrugs in R&D2019
Multikinase Abl/DDR/Src Inhibition Produces Optimal Effects for Tyrosine Kinase Inhibition in Neurodegeneration.
Article in Drugs in R&D, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Anticancer drugs repurposed for Alzheimer's disease: a systematic review.Alzheimer's research & therapy · 2021Pooled it
- Nilotinib treatment outcomes in autosomal dominant spinocerebellar ataxia over one year.Scientific reports · 2024Trial
- Long-Term Safety and Clinical Effects of Nilotinib in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021Trial
- Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial.JAMA neurology · 2020Trial
- Tyrosine kinase inhibitor use and risk of neurodegenerative disease: A Swedish population-based cohort study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Synergistic Effects of Multi-Kinase Inhibition onBiomedicines · 2026Article
- α-Synuclein in Parkinson's Disease: From Bench to Bedside.Medicinal research reviews · 2025Review
- Modulation of Peripheral Mast Cell and Brain Microglia Axis via Kinase Inhibition.Metabolites · 2025Article
- c-KIT inhibitors reduce pathology and improve behavior in the Tg(SwDI) model of Alzheimer's disease.Life science alliance · 2024Article
- Nilotinib as a Prospective Treatment for Alzheimer's Disease: Effect on Proteins Involved in Neurodegeneration and Neuronal Homeostasis.Life (Basel, Switzerland) · 2024Article
- Neuroprotective Activity of a Non-Covalent Imatinib+TP10 Conjugate in HT-22 Neuronal Cells In Vitro.Pharmaceutics · 2024Article
- Multifaceted collagen-DDR1 signaling in cancer.Trends in cell biology · 2024Review
- Identification of Ureidocoumarin-Based Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors via Drug Repurposing Approach, Biological Evaluation, and In Silico Studies.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.Frontiers in dementia · 2024Review
- Cancer drugs with high repositioning potential for Alzheimer's disease.Expert opinion on emerging drugs · 2023Review
- Review
- Inhibition of discoidin domain receptor (DDR)-1 with nilotinib alters CSF miRNAs and is associated with reduced inflammation and vascular fibrosis in Alzheimer's disease.Journal of neuroinflammation · 2023Article
- Pathophysiology and Neuroimmune Interactions Underlying Parkinson's Disease and Traumatic Brain Injury.International journal of molecular sciences · 2023Review
- Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients.Metabolites · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesInhibition of Abelson (Abl) tyrosine kinase as a therapeutic target has been gaining attention in neurodegeneration. Post-mortem Alzheimer's and Parkinson's disease brains show that the levels of several other tyrosine kinases, including Discoidin Domain Receptors (DDR1/2) are elevated. Knockdown of these tyrosine kinases with shRNA reduces neurotoxic proteins, including alpha-synuclein, beta-amyloid and tau.
methodsDirect profiling of the pharmacokinetics of multi-kinase inhibitors Nilotinib, Bosutinib, Bafetinib, Radotinib and LCB-03-0110 shows differential levels of brain penetration but the ability of these agents to reduce toxic proteins is independent of brain concentration and selectivity to Abl.
resultsOur results indicate that the effective dose of Nilotinib has the lowest plasma:brain ratio (1%) followed by Bosutinib and Radotinib (5%), Bafetinib (12%) and LCB-03-0110 (12%). However, similar doses of multi-kinase Abl/DDR inhibitor Nilotinib, DDR/Src inhibitor LCB-03-0110 and Abl/Src inhibitor Bosutinib were much more effective than the more selective Abl inhibitors Radotinib and Bafetinib. Taken together, these data suggest that a multi-kinase target that includes Abl and other tyrosine kinases (DDRs, and Src) may offer more advantages alleviating neurodegenerative pathologies than the absolute CNS drug concentration and selectivity to Abl.
conclusionDDRs and Src are other potential co-targets with Abl in neurodegeneration.
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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.