ArticleLife science alliance2019
Phenotypic proteomic profiling identifies a landscape of targets for circadian clock-modulating compounds.
Article in Life science alliance, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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
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
7 citing papers in PubMed, 19 citations in OpenAlex.
- Cell painting and thermal proteome profiling for inference of drug targets and mechanism of action.Molecular systems biology · 2026Article
- Activity-based chemoproteomic profiling reveals the active kinome ofFrontiers in pharmacology · 2025Article
- Integrated bioinformatics and interaction analysis to advance chronotherapies for mental disorders.Frontiers in pharmacology · 2024Article
- Single-cell transcriptomics and cell-specific proteomics reveals molecular signatures of sleep.Communications biology · 2022Article
- Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity.Communications biology · 2020Article
- Small Molecules Targeting Biological Clock; A Novel Prospective for Anti-Cancer Drugs.Molecules (Basel, Switzerland) · 2020Review
- An Integrated Quantitative Proteomics Workflow for Cancer Biomarker Discovery and Validation in Plasma.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Determining the exact targets and mechanisms of action of drug molecules that modulate circadian rhythms is critical to develop novel compounds to treat clock-related disorders. Here, we have used phenotypic proteomic profiling (PPP) to systematically determine molecular targets of four circadian period-lengthening compounds in human cells. We demonstrate that the compounds cause similar changes in phosphorylation and activity of several proteins and kinases involved in vital pathways, including MAPK, NGF, B-cell receptor, AMP-activated protein kinases (AMPKs), and mTOR signaling. Kinome profiling further indicated inhibition of CKId, ERK1/2, CDK2/7, TNIK, and MST4 kinases as a common mechanism of action for these clock-modulating compounds. Pharmacological or genetic inhibition of several convergent kinases lengthened circadian period, establishing them as novel circadian targets. Finally, thermal stability profiling revealed binding of the compounds to clock regulatory kinases, signaling molecules, and ubiquitination proteins. Thus, phenotypic proteomic profiling defines novel clock effectors that could directly inform precise therapeutic targeting of the circadian system in humans.
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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.