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Compound class: Synthetic organic
Comment: GSK8612 is a selective inhibitor of Tank-binding kinase 1 (TBK1) . TBK1 is a noncanonical member of the IκB kinase (IKK) family that is involved in regulating signalling pathways in several physiological processes including innate immunity [1,3], oncogenesis, energy homeostasis, autophagy, and neuroinflammation. TBK1 is activated downstream of TLR3/TLR4 ligand engagement, via the adaptor protein TRIF. This subsequently results in IRF3 phosphorylation and culminates in IFNβ secretion from cell types including dendritic cells and macrophages. Dysregulated TBK1 activity is associated with autoimmune disorders, hence pharmacological inhibitors are considered for the treatment of (auto)inflammatory diseases.
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
1. Tanaka Y, Chen ZJ. (2012)
STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway.
Sci Signal, 5 (214): ra20. [PMID:22394562]
2. Thomson DW, Poeckel D, Zinn N, Rau C, Strohmer K, Wagner AJ, Graves AP, Perrin J, Bantscheff M, Duempelfeld B et al.. (2019)
Discovery of GSK8612, a Highly Selective and Potent TBK1 Inhibitor.
ACS Med Chem Lett, 10 (5): 780-785. DOI: 10.1021/acsmedchemlett.9b00027 [PMID:31097999]
3. Zhan Z, Cao H, Xie X, Yang L, Zhang P, Chen Y, Fan H, Liu Z, Liu X. (2015)
Phosphatase PP4 Negatively Regulates Type I IFN Production and Antiviral Innate Immunity by Dephosphorylating and Deactivating TBK1.
J Immunol, 195 (8): 3849-57. [PMID:26363053]