ArticleThe Journal of biological chemistry2020
A CLOCK-binding small molecule disrupts the interaction between CLOCK and BMAL1 and enhances circadian rhythm amplitude.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 79 citations in OpenAlex.
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- Advances in monitoring mammalian circadian components and their rhythms using reporter systems.RSC chemical biology · 2026Review
- The circadian clock controls hepatic stellate cell activation via a BMAL1/CK1ε/REV-ERBα/transgelin signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The CLOCK-BMAL1 complex in circadian regulation: structure, mechanisms, and therapeutic targeting.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Small-Molecule Modulation of the Circadian Clock in Cancer and Aging.Molecules (Basel, Switzerland) · 2026Review
- Small Molecule Regulation of CLOCK:BMAL1 DNA Binding Activity.bioRxiv : the preprint server for biology · 2026Article
- A temporal dialogue between the circadian clock and chronic inflammatory diseases.Disease models & mechanisms · 2026Review
- Conserved structural motifs in PAS, LOV, and CRY proteins regulate circadian rhythms and are therapeutic targets.FEBS letters · 2026Review
- Integration of circadian and hypoxia signaling via non-canonical heterodimerization.FEBS letters · 2026Review
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- Research Progress of BMAL1 in Heart Failure.Journal of the American Heart Association · 2025Review
- Circadian genesJournal of Zhejiang University. Science. B · 2025Review
- Time of Day-Dependent Responses to Cisplatin Treatment in a Male Mouse Model of Hepatoma.Journal of biological rhythms · 2025Article
- Role of circadian CLOCK signaling in cellular senescence.Biogerontology · 2025Review
- Clock pathway inhibitor overcomes tumor immune-exclusion via regulation of fibrocyte differentiation.NPJ precision oncology · 2025Article
- Pharmacological targeting of BMAL1 modulates circadian and immune pathways.Nature chemical biology · 2025Article
- Natural Compounds that Modulate Circadian Rhythms.Current topics in medicinal chemistry · 2025Review
- The SnackerTracker: A novel home-cage monitoring device for measuring food-intake and food-seeking behaviour in mice.Wellcome open research · 2025Article
- Circadian rhythm regulates the function of immune cells and participates in the development of tumors.Cell death discovery · 2024Review
- PAS Dimerization at the Nexus of the Mammalian Circadian Clock.Journal of molecular biology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proper function of many physiological processes requires a robust circadian clock. Disruptions of the circadian clock can result in metabolic diseases, mood disorders, and accelerated aging. Therefore, identifying small molecules that specifically modulate regulatory core clock proteins may potentially enable better management of these disorders. In this study, we applied a structure-based molecular-docking approach to find small molecules that specifically bind to the core circadian regulator, the transcription factor circadian locomotor output cycles kaput (CLOCK). We identified 100 candidate molecules by virtual screening of ∼2 million small molecules for those predicted to bind closely to the interface in CLOCK that interacts with its transcriptional co-regulator, Brain and muscle Arnt-like protein-1 (BMAL1). Using a mammalian two-hybrid system, real-time monitoring of circadian rhythm in U2OS cells, and various biochemical assays, we tested these compounds experimentally and found one, named CLK8, that specifically bound to and interfered with CLOCK activity. We show that CLK8 disrupts the interaction between CLOCK and BMAL1 and interferes with nuclear translocation of CLOCK both
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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.