ArticleJournal of medicinal chemistry2014
Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 117 citations in OpenAlex.
- TDP-43-immunity-microbiota axis in amyotrophic lateral sclerosis: A potential pathogenic mechanism.Neural regeneration research · 2026Article
- Contemporary trends on the kinase inhibitors with special reference to quinoxaline derivatives.Molecular diversity · 2026Review
- TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.Biochemical Society transactions · 2026Review
- Beyond motor neurons: peripheral TDP-43 pathology in skeletal muscle and intramuscular nerves in amyotrophic lateral sclerosis.Brain communications · 2026Review
- Neurocritical progression in amyotrophic lateral sclerosis: pathological relevance and validation.Open life sciences · 2026Review
- Molecular mechanisms and consequences of TDP-43 phosphorylation in neurodegeneration.Molecular neurodegeneration · 2025Review
- Druggable cavities and allosteric modulators of the cell division cycle 7 (CDC7) kinase.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Identification of novel neuroprotectants against vincristine-induced neurotoxicity in iPSC-derived neurons.Cellular and molecular life sciences : CMLS · 2024Article
- Identification of novel neuroprotectants against vincristine-induced neurotoxicity in iPSC-derived neurons.Research square · 2024Article
- Structural Investigations on 2-Amidobenzimidazole Derivatives as New Inhibitors of Protein Kinase CK1 Delta.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Small molecules targeting different cellular pathologies for the treatment of amyotrophic lateral sclerosis.Medicinal research reviews · 2023Review
- Dual Anta-Inhibitors Targeting Protein Kinase CK1δ and AMolecules (Basel, Switzerland) · 2023Article
- Progranulin Deficiency Induces Mitochondrial Dysfunction in Frontotemporal Lobar Degeneration with TDP-43 Inclusions.Antioxidants (Basel, Switzerland) · 2023Article
- "Dual Anta-Inhibitors" of the APharmaceuticals (Basel, Switzerland) · 2023Article
- TTBK1 and CK1 inhibitors restore TDP-43 pathology and avoid disease propagation in lymphoblast from Alzheimer's disease patients.Frontiers in molecular neuroscience · 2023Article
- MBC and ECBL libraries: outstanding tools for drug discovery.Frontiers in pharmacology · 2023Article
- Functional insights from targeted imaging BACE1: the first near-infrared fluorescent probe for Alzheimer's disease diagnosis.Biomaterials research · 2022Article
- Discovery of Mitophagy Inhibitors with Therapeutic Potential in Different Familial Amyotrophic Lateral Sclerosis Mutations.International journal of molecular sciences · 2022Article
- Riluzole-Rasagiline Hybrids: Toward the Development of Multi-Target-Directed Ligands for Amyotrophic Lateral Sclerosis.ACS chemical neuroscience · 2022Article
- Altered TDP-43 Structure and Function: Key Insights into Aberrant RNA, Mitochondrial, and Cellular and Systemic Metabolism in Amyotrophic Lateral Sclerosis.Metabolites · 2022Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor neurons in cortex, brain stem, and spinal cord die progressively, resulting in muscle wasting, paralysis, and death. Currently, effective therapies for ALS are lacking; however, identification of pathological TAR DNA-binding protein 43 (TDP-43) as the hallmark lesion in sporadic ALS suggests new therapeutic targets for pharmacological intervention. Pathological TDP-43 phosphorylation appears to drive the onset and progression of ALS and may result from upregulation of the protein kinase CK-1 in affected neurons, resulting in postranslational TDP-43 modification. Consequently, brain penetrant specific CK-1 inhibitors may provide a new therapeutic strategy for treating ALS and other TDP-43 proteinopathies. Using a chemical genetic approach, we report the discovery and further optimization of a number of potent CK-1δ inhibitors. Moreover, these small heterocyclic molecules are able to prevent TDP-43 phosphorylation in cell cultures, to increase Drosophila lifespan by reduction of TDP-43 neurotoxicity, and are predicted to cross the blood-brain barrier. Thus, N-(benzothiazolyl)-2-phenyl-acetamides are valuable drug candidates for further studies and may be a new therapeutic approach for ALS and others pathologies in which TDP-43 is involved.
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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.