ArticleJournal of biomolecular screening2015
Identification of Small-Molecule Inhibitors of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels.
Article in Journal of biomolecular screening, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- A Molecular Framework for Delirium.The Neurohospitalist · 2024Review
- Characterization of hyperpolarization-activated cyclic nucleotide-gated channels in oligodendrocytes.Frontiers in cellular neuroscience · 2024Article
- Seizures, behavioral deficits, and adverse drug responses in two new genetic mouse models ofeLife · 2022Article
- Discovery of a small-molecule inhibitor of the TRIP8b-HCN interaction with efficacy in neurons.The Journal of biological chemistry · 2022Article
- Regulation of HCN Channels by Protein Interactions.Frontiers in physiology · 2022Review
- Hippocampal cAMP regulates HCN channel function on two time scales with differential effects on animal behavior.Science translational medicine · 2021Article
- The structure and function of TRIP8b, an auxiliary subunit of hyperpolarization-activated cyclic-nucleotide gated channels.Channels (Austin, Tex.) · 2020Review
- Modulation of thalamocortical oscillations by TRIP8b, an auxiliary subunit for HCN channels.Brain structure & function · 2018Article
- Allostery between two binding sites in the ion channel subunit TRIP8b confers binding specificity to HCN channels.The Journal of biological chemistry · 2017Article
- HCN Channel Targets for Novel Antidepressant Treatment.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Review
- HCN-channel dendritic targeting requires bipartite interaction with TRIP8b and regulates antidepressant-like behavioral effects.Molecular psychiatry · 2017Article
- Animal models suggest the TRIP8b-HCN interaction is a therapeutic target for major depressive disorder.Expert opinion on therapeutic targets · 2017Article
- Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b.Journal of visualized experiments : JoVE · 2016Article
- Quantitative Trait Loci and a Novel Genetic Candidate for Fear Learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels function in the brain to limit neuronal excitability. Limiting the activity of these channels has been proposed as a therapy for major depressive disorder, but the critical role of HCN channels in cardiac pacemaking has limited efforts to develop therapies directed at the channel. Previous studies indicated that the function of HCN is tightly regulated by its auxiliary subunit, tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), which is not expressed in the heart. To target the function of the HCN channel in the brain without affecting the channel's function in the heart, we propose disrupting the interaction between HCN and TRIP8b. We developed a high-throughput fluorescence polarization (FP) assay to identify small molecules capable of disrupting this interaction. We used this FP assay to screen a 20,000-compound library and identified a number of active compounds. The active compounds were validated using an orthogonal AlphaScreen assay to identify one compound (0.005%) as the first confirmed hit for inhibiting the HCN-TRIP8b interaction. Identifying small molecules capable of disrupting the interaction between HCN and TRIP8b should enable the development of new research tools and small-molecule therapies that could benefit patients with depression.
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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.