ArticleMolecular systems biology2019
Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy.
Article in Molecular systems biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
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- Optimizing oral contraceptive timing: Daytime intake reduces doses and enhances efficacy.PLoS computational biology · 2026Article
- Markovian state models uncover casein kinase 1 dynamics that govern circadian period.Biophysical journal · 2025Article
- Cardiogenic and chronobiological mechanisms in seizure-induced sinus arrhythmias.PLoS computational biology · 2025Article
- Phosphorylation of DNA-binding domains of CLOCK-BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Circadian regulation of sinoatrial nodal cell pacemaking function: Dissecting the roles of autonomic control, body temperature, and local circadian rhythmicity.PLoS computational biology · 2024Article
- The Opioid Receptor Influences Circadian Rhythms in Human Keratinocytes through the β-Arrestin Pathway.Cells · 2024Article
- The circadian clock of the bacteriumScience advances · 2023Article
- An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells.NPJ systems biology and applications · 2023Article
- Spatially coordinated collective phosphorylation filters spatiotemporal noises for precise circadian timekeeping.iScience · 2023Article
- Rhythmic transcription of Bmal1 stabilizes the circadian timekeeping system in mammals.Nature communications · 2022Article
- Biochemical mechanisms of period control within the mammalian circadian clock.Seminars in cell & developmental biology · 2022Review
- Complex dynamics in a synchronized cell-free genetic clock.Nature communications · 2022Article
- Mathematical analysis of robustness of oscillations in models of the mammalian circadian clock.PLoS computational biology · 2022Article
- An Anticipatory Scheme for the Model Predictive Control of Circadian Phase for Expected Environmental Light Changes.IEEE control systems letters · 2022Article
- Modelling of plant circadian clock for characterizing hypocotyl growth under different light quality conditions.In silico plants · 2022Article
- A stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light.Scientific reports · 2021Article
- Complementary phase responses via functional differentiation of dual negative feedback loops.PLoS computational biology · 2021Article
- Circadian Rhythms of Early Afterdepolarizations and Ventricular Arrhythmias in a Cardiomyocyte Model.Biophysical journal · 2021Article
- Multiple random phosphorylations in clock proteins provide long delays and switches.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
In mammals, the master circadian clock synchronizes daily rhythms of physiology and behavior with the day-night cycle. Failure of synchrony, which increases the risk for numerous chronic diseases, can be treated by phase adjustment of the circadian clock pharmacologically, for example, with melatonin, or a CK1δ/ε inhibitor. Here, using in silico experiments with a systems pharmacology model describing molecular interactions, and pharmacokinetic and behavioral experiments in cynomolgus monkeys, we find that the circadian phase delay caused by CK1δ/ε inhibition is more strongly attenuated by light in diurnal monkeys and humans than in nocturnal mice, which are common preclinical models. Furthermore, the effect of CK1δ/ε inhibition strongly depends on endogenous PER2 protein levels, which differs depending on both the molecular cause of the circadian disruption and the patient's lighting environment. To circumvent such large interindividual variations, we developed an adaptive chronotherapeutics to identify precise dosing regimens that could restore normal circadian phase under different conditions. Our results reveal the importance of photosensitivity in the clinical efficacy of clock-modulating drugs, and enable precision medicine for circadian disruption.
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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.