ArticleChemMedChem2011
Identification of a glycogen synthase kinase-3β inhibitor that attenuates hyperactivity in CLOCK mutant mice.
Article in ChemMedChem, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Face and predictive validity of the ClockΔ19 mouse as an animal model for bipolar disorder: a systematic review.Molecular psychiatry · 2018Pooled it
- Different Protocols of Circadian Rhythm Disruptions Differentially Affect Locomotor Activity, and Anxiety- and Compulsive-Like Behaviors in Male vs. Female Wistar Rats along with the Significant Involvement of GSK-3β in Females.Molecular neurobiology · 2025Article
- Bisindolyl Maleimides and Indolylmaleimide Derivatives-A Review of Their Synthesis and Bioactivity.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology.Bipolar disorders · 2022Review
- Inhibition of glycogen synthase kinase 3 by lithium, a mechanism in search of specificity.Frontiers in molecular neuroscience · 2022Review
- A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3.Biochemistry. Biokhimiia · 2021Review
- Glycogen Synthase Kinase-3 Inhibitors: Preclinical and Clinical Focus on CNS-A Decade Onward.Frontiers in molecular neuroscience · 2021Review
- Pharmacological Manipulation of the Circadian Clock: A Possible Approach to the Management of Bipolar Disorder.CNS drugs · 2019Review
- Wnt and GSK3 Signaling Pathways in Bipolar Disorder: Clinical and Therapeutic Implications.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2017Review
- Epigenetic mechanisms in mood disorders: targeting neuroplasticity.Neuroscience · 2014Review
- Wnt and lithium: a common destiny in the therapy of nervous system pathologies?Cellular and molecular life sciences : CMLS · 2014Review
- Differential effects of glycogen synthase kinase 3 (GSK3) inhibition by lithium or selective inhibitors in the central nervous system.Naunyn-Schmiedeberg's archives of pharmacology · 2013Article
- Manipulating the sleep-wake cycle and circadian rhythms to improve clinical management of major depression.BMC medicine · 2013Article
- The wnt pathway in mood disorders.Current neuropharmacology · 2012Article
- Structure-guided design of a highly selective glycogen synthase kinase-3β inhibitor: a superior neuroprotective pyrazolone showing antimania effects.ChemMedChem · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Bipolar disorder is characterized by a cycle of mania and depression, which affects approximately 5 million people in the United States. Current treatment regimes include the so-called "mood-stabilizing drugs", such as lithium and valproate that are relatively dated drugs with various known side effects. Glycogen synthase kinase-3β (GSK-3β) plays a central role in regulating circadian rhythms, and lithium is known to be a direct inhibitor of GSK-3β. We designed a series of second generation benzofuran-3-yl-(indol-3-yl)maleimides containing a piperidine ring that possess IC₅₀ values in the range of 4 to 680 nM against human GSK-3β. One of these compounds exhibits reasonable kinase selectivity and promising preliminary absorption, distribution, metabolism, and excretion (ADME) data. The administration of this compound at doses of 10 to 25 mg kg⁻¹ resulted in the attenuation of hyperactivity in amphetamine/chlordiazepoxide-induced manic-like mice together with enhancement of prepulse inhibition, similar to the effects found for valproate (400 mg kg⁻¹) and the antipsychotic haloperidol (1 mg kg⁻¹). We also tested this compound in mice carrying a mutation in the central transcriptional activator of molecular rhythms, the CLOCK gene, and found that the same compound attenuates locomotor hyperactivity in response to novelty. This study further demonstrates the use of inhibitors of GSK-3β in the treatment of manic episodes of bipolar/mood disorders, thus further validating GSK-3β as a relevant therapeutic target in the identification of new therapies for bipolar patients.
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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.