| Use case/disease area | Compound/inhibitor or intervention | Mechanism (TBK1/IKKε etc) | Model/system | Key quantitative/statistical details | Notes/limitations | Source (with DOI URL and date) |
|---|---|---|---|---|---|---|
| COVID-19 / SARS-CoV-2 hyper-inflammation | Idronoxil (IDX) | Small-molecule inhibitor that suppresses TBK1/IKKε signaling by destabilizing TBK1/IKKε protein complexes; proposed to limit harmful inflammatory signaling rather than directly target viral replication (pqac-00000013, pqac-00000014) | Murine SARS-CoV-2 immunopathology model; supporting cell-based assays including Vero infection assay and multiple innate-immune reporter/cell systems (pqac-00000013, pqac-00000014) | Preliminary Phase I rectal-delivery study reported good tolerability in **38 hospitalized moderate COVID-19 patients**; human safety profile cited as established in **>600 cancer patients**; antiviral assay used **MOI 0.002**, with IDX tested in **3-fold serial dilution from 50 μM** (Remdesivir from 20 μM) (pqac-00000013) | Quantitative efficacy values are not provided in the extracted text; translational rationale is stronger than direct clinical efficacy evidence here; effects may reflect broader TBK1/IKKε pathway modulation (pqac-00000013, pqac-00000014) | Ullah et al., *Nature Communications*, 2023-09, https://doi.org/10.1038/s41467-023-41381-9 (pqac-00000013, pqac-00000014) |
| Innate immune / cytoskeletal signaling; tumor immunity | MRT67307 | Pharmacologic TBK1 inhibitor used to block TBK1 kinase activity; in this context suppresses Zyxin phosphorylation downstream of STING/MAVS-TBK1 signaling (pqac-00000011, pqac-00000015) | Primary macrophages and cell systems stimulated by HSV-1, SeV, poly(I:C), diABZI, or cGAMP; focal-adhesion/TBK1 puncta imaging and immunoblot analyses (pqac-00000011, pqac-00000015) | Immunofluorescence quantification used **n = 4 per group** for panel E and **n = 3 per group** for panel F; inhibitor treatment eliminated inducible **pZyxin(S142/S143)** in parallel with loss of **pIRF3**, while not eliminating TBK1 S172 phosphorylation signal in the reported assays (pqac-00000011) | Primarily a mechanistic research tool, not a clinically validated TBK1 therapy; extracted text does not provide dose-response or in vivo human data (pqac-00000011, pqac-00000015) | Zhou et al., *The EMBO Journal*, 2024-09, https://doi.org/10.1038/s44318-024-00244-9 (pqac-00000011, pqac-00000015) |
| Innate immune / cytoskeletal signaling; tumor immunity | BX795 | TBK1 inhibitor used experimentally to abrogate TBK1 activity and downstream Zyxin phosphorylation in STING/MAVS-TBK1-Zyxin pathway studies (pqac-00000011, pqac-00000015) | Same macrophage and cell-signaling systems as above; nucleic-acid sensing and focal-adhesion remodeling assays (pqac-00000011, pqac-00000015) | Inhibiting TBK1 with **BX795 or MRT67307** eliminated Zyxin phosphorylation, paralleling inhibition of IRF3 phosphorylation during HSV-1/SeV/poly(I:C) responses; figure-based quantification used **n = 3-4** independent experiments depending on panel (pqac-00000011) | Widely used but known in the field as a multi-kinase tool compound; extracted text here focuses on mechanistic inference, not therapeutic translation (pqac-00000011, pqac-00000015) | Zhou et al., *The EMBO Journal*, 2024-09, https://doi.org/10.1038/s44318-024-00244-9 (pqac-00000011, pqac-00000015) |
| Painful diabetic neuropathy (PDN) | Amlexanox (AMX) | TBK1 inhibitor proposed to reduce microglial pyroptosis and noncanonical NF-κB/NLRP3-linked inflammatory signaling in PDN (paper describes it as a TBK1 inhibitor) (pqac-00000009) | Mouse PDN models including streptozotocin-induced T1DM and db/db T2DM-related neuropathy; spinal dorsal horn/microglial analyses plus behavioral and nerve-injury readouts (pqac-00000009) | Power calculation used **α = 0.05**, **power = 0.8**, and **sample size = 5/group** for repeated behavioral measures; intrathecal **TBK1 siRNA 10 μg/mouse** and **Ac-YVAD-cmk 10 nmol/mouse** were used in intervention experiments; systemic AMX was reported to improve peripheral nerve injury (pqac-00000009) | The extracted pages do not provide a specific AMX dose or effect size; evidence is preclinical and includes siRNA plus inhibitor data rather than a standalone drug-development package (pqac-00000009) | Liao et al., *Cell Communication and Signaling*, 2024-07, https://doi.org/10.1186/s12964-024-01723-6 (pqac-00000009) |
| Frontotemporal dementia (FTD) genetics / patient stratification | TBK1 variant screening and functional characterization | Human genetic association plus functional assays of TBK1 variants affecting autophosphorylation and OPTN-related autophagy signaling (pqac-00000019, pqac-00000020, pqac-00000021) | Chinese FTD cohort and meta-analysis; in vitro HEK293T functional assays for TBK1 mutants and OPTN phosphorylation/complex formation (pqac-00000019, pqac-00000020, pqac-00000021) | In the cohort, **61/261 (23.4%)** carried potential causative FTD-gene variants; **TBK1 variants were found in 7 patients**; pooled Chinese FTD meta-analysis estimated TBK1 mutation frequency at **2.0% (95% CI 1.0%-3.1%)**; one excerpt also reports **19/751** positive cases overall; functional assays showed **I37T** and **E232Q** had decreased TBK1 autophosphorylation, and **I37T** reduced OPTN phosphorylation, while **E696G** increased OPTN-TBK1 complex formation (pqac-00000019, pqac-00000020, pqac-00000021) | Translational value is strongest for diagnosis/genetic stratification rather than immediate drug intervention; some cohort/count discrepancies across excerpts likely reflect different filtering definitions (all variants vs pathogenic subsets) and should be interpreted carefully (pqac-00000019, pqac-00000020, pqac-00000021, pqac-00000022) | Nan et al., *Alzheimer's Research & Therapy*, 2024-06, https://doi.org/10.1186/s13195-024-01493-w (pqac-00000019, pqac-00000020, pqac-00000021, pqac-00000022) |


*Table: This table summarizes translationally relevant TBK1 evidence across infection, inflammation, neuropathy, and neurodegenerative genetics. It highlights compounds, mechanisms, models, and quantitative details that are useful for prioritizing TBK1-related therapeutic or biomarker opportunities.*