Small molecules targeting casein kinase 1 to directly entrain peripheral circadian clocks in brain microglia without light input or sleep modifications
Auto-built from this analysis's top knowledge-graph edges.
graph TD
ARNTL["ARNTL"] -->|transcriptionally| NLRP3["NLRP3"]
circadian_disruption["circadian disruption"] -->|causes| neuroinflammation["neuroinflammation"]
IL1R1["IL1R1"] -->|mediates| Microglial_priming["Microglial priming"]
anti_TNF_drugs["anti-TNF drugs"] -->|targets| neuroinflammation_1["neuroinflammation"]
inflammation["inflammation"] -->|causes| Microglial_priming_2["Microglial priming"]
microglial_priming["microglial_priming"] -->|causes| neurodegeneration["neurodegeneration"]
NR1D1["NR1D1"] -->|represses| NFKB1["NFKB1"]
IL1R1_3["IL1R1"] -->|mediates| microglial_priming_4["microglial_priming"]
circadian_disruption_5["circadian_disruption"] -->|causes| neuroinflammation_6["neuroinflammation"]
CSNK1D["CSNK1D"] -->|phosphorylates| PER1["PER1"]
MMP9["MMP9"] -->|remodels| extracellular_matrix["extracellular_matrix"]
IL1R1_7["IL1R1"] -->|modulates| positive_feedback_loops["positive_feedback_loops"]
style ARNTL fill:#ce93d8,stroke:#333,color:#000
style NLRP3 fill:#ce93d8,stroke:#333,color:#000
style circadian_disruption fill:#4fc3f7,stroke:#333,color:#000
style neuroinflammation fill:#4fc3f7,stroke:#333,color:#000
style IL1R1 fill:#ce93d8,stroke:#333,color:#000
style Microglial_priming fill:#4fc3f7,stroke:#333,color:#000
style anti_TNF_drugs fill:#4fc3f7,stroke:#333,color:#000
style neuroinflammation_1 fill:#4fc3f7,stroke:#333,color:#000
style inflammation fill:#4fc3f7,stroke:#333,color:#000
style Microglial_priming_2 fill:#4fc3f7,stroke:#333,color:#000
style microglial_priming fill:#4fc3f7,stroke:#333,color:#000
style neurodegeneration fill:#ef5350,stroke:#333,color:#000
style NR1D1 fill:#ce93d8,stroke:#333,color:#000
style NFKB1 fill:#ce93d8,stroke:#333,color:#000
style IL1R1_3 fill:#ce93d8,stroke:#333,color:#000
style microglial_priming_4 fill:#4fc3f7,stroke:#333,color:#000
style circadian_disruption_5 fill:#4fc3f7,stroke:#333,color:#000
style neuroinflammation_6 fill:#4fc3f7,stroke:#333,color:#000
style CSNK1D fill:#ce93d8,stroke:#333,color:#000
style PER1 fill:#ce93d8,stroke:#333,color:#000
style MMP9 fill:#ce93d8,stroke:#333,color:#000
style extracellular_matrix fill:#81c784,stroke:#333,color:#000
style IL1R1_7 fill:#ce93d8,stroke:#333,color:#000
style positive_feedback_loops fill:#4fc3f7,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for CSNK1D yet. Search RCSB →
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for CSNK1D.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF CSNK1 inhibitor is administered at 6 different circadian time points (CT2, CT6, CT10, CT14, CT18, CT22) THEN a dose-dependent Phase Response Curve (PRC) will be generated showing predictable phase | Maximum phase advance of 3.5±0.8h at CT18-20 and maximum phase delay of 4.2±1.1h at CT8-10; PRC amplitude >2x baseline rhythm amplitude; ED50 < 500nM for CSNK1 | — no observation — | pending | 0.70 |
| IF pharmacological CSNK1 inhibitor (PF-670462, 10mg/kg, i.p.) is administered to adult mice during constant darkness THEN a measurable phase shift in microglial PER2::LUC bioluminescence will be obser | Phase shift of 2-6 hours in microglial PER2::LUC peak expression relative to vehicle controls, with significant changes in BMAL1::LUC anti-phase oscillations (p | — no observation — | pending | 0.75 |