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Synonyms: compound 32 [PMID: 26861551]
Compound class: Synthetic organic
Comment: GSK2245035 is reported as a selective Toll-like receptor 7 (TLR7) agonist, with potential clinical action as an intranasally administered anti-asthmatic . It is Example 22 claimed in patent WO2010018133 .
The TLR7- IFNα pathway is a novel pathway being investigated for pharmacological intervention in allergic asthma.
|In vivo findings disclosed in WO2010018133 report that GSK2245035 (Example 22) induces IFNα production, with mean serum levels reaching 21029 pg/ml (none detected in control mice) . Early clinical trial results show clear target engagement at a dose of 20ng (as detected by local and peripheral increase of IFN-gamma-inducible protein-10) and an accceptable safety profile doses acheiving a local TLR7-mediated immune response . Doses above 100ng were associated with undesireable cytokine release syndrome-related symptoms.
Direct binding assays have not been performed for this compound, rather its engagement with TLR7 has been assessed in functional assays measuring ligand-induced increases in downstream cytokine production/release . An EC50 of ~4.5nM for IFNα production in PBMCs is reported .
|Selectivity at catalytic receptors|
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