ArticleBiological psychiatry2018
Novel Small-Molecule Inhibitors of Protein Kinase C Epsilon Reduce Ethanol Consumption in Mice.
Article in Biological psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- A small molecule PKCε inhibitor reduces hyperalgesia induced by paclitaxel or opioid withdrawal.JCI insight · 2025Article
- Synaptic Effects Induced by Alcohol.Current topics in behavioral neurosciences · 2025Review
- Brain-specific serine/threonine-protein kinase 1 is a substrate of protein kinase C epsilon involved in sex-specific ethanol and anxiety phenotypes.Addiction biology · 2024Article
- Cell cycle responses to Topoisomerase II inhibition: Molecular mechanisms and clinical implications.The Journal of cell biology · 2023Review
- Alcohol Dependence Modulates Amygdalar mTORC2 and PKCε Expression in a Rodent Model.Nutrients · 2023Article
- Article
- Alcohol and the brain: from genes to circuits.Trends in neurosciences · 2021Review
- Bidirectional sex-dependent regulation of α6 and β3 nicotinic acetylcholine receptors by protein kinase Cε.Addiction biology · 2021Article
- Leveraging genetic data to investigate molecular targets and drug repurposing candidates for treating alcohol use disorder and hepatotoxicity.Drug and alcohol dependence · 2020Article
- From Pleasure to Pain, and Back Again: The Intricate Relationship Between Alcohol and Nociception.Alcohol and alcoholism (Oxford, Oxfordshire) · 2019Review
- Driving the Downward Spiral: Alcohol-Induced Dysregulation of Extended Amygdala Circuits and Negative Affect.Alcoholism, clinical and experimental research · 2019Review
- Differential Regulation of Gene Expression in Lung Cancer Cells by Diacyglycerol-Lactones and a Phorbol Ester Via Selective Activation of Protein Kinase C Isozymes.Scientific reports · 2019Article
- The center of the emotional universe: Alcohol, stress, and CRF1 amygdala circuitry.Alcohol (Fayetteville, N.Y.) · 2018Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundDespite the high cost and widespread prevalence of alcohol use disorders, treatment options are limited, underscoring the need for new, effective medications. Previous results using protein kinase C epsilon (PKCε) knockout mice, RNA interference against PKCε, and peptide inhibitors of PKCε predict that small-molecule inhibitors of PKCε should reduce alcohol consumption in humans.
methodsWe designed a new class of PKCε inhibitors based on the Rho-associated protein kinase (ROCK) inhibitor Y-27632. In vitro kinase and binding assays were used to identify the most potent compounds. Their effects on ethanol-stimulated synaptic transmission; ethanol, sucrose, and quinine consumption; ethanol-induced loss of righting; and ethanol clearance were studied in mice.
resultsWe identified two compounds that inhibited PKCε with Ki <20 nM, showed selectivity for PKCε over other kinases, crossed the blood-brain barrier, achieved effective concentrations in mouse brain, prevented ethanol-stimulated gamma-aminobutyric acid release in the central amygdala, and reduced ethanol consumption when administered intraperitoneally at 40 mg/kg in wild-type but not in Prkce
conclusionsThese results identify lead compounds for development of PKCε inhibitors that reduce alcohol consumption.
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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.