GSK2245035   Click here for help

GtoPdb Ligand ID: 9254

Synonyms: compound 32 [PMID: 26861551]
Immunopharmacology Ligand
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 [2]. It is Example 22 claimed in patent WO2010018133 [3].

The TLR7- IFNα pathway is a novel pathway being investigated for pharmacological intervention in allergic asthma.
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 102.06
Molecular weight 390.27
XLogP 3.19
No. Lipinski's rules broken 0
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Canonical SMILES CCCC(Oc1nc(N)c2c(n1)n(CCCCCN1CCCCC1)c(=O)[nH]2)C
Isomeric SMILES CCC[C@@H](Oc1nc(N)c2c(n1)n(CCCCCN1CCCCC1)c(=O)[nH]2)C
InChI InChI=1S/C20H34N6O2/c1-3-10-15(2)28-19-23-17(21)16-18(24-19)26(20(27)22-16)14-9-5-8-13-25-11-6-4-7-12-25/h15H,3-14H2,1-2H3,(H,22,27)(H2,21,23,24)/t15-/m0/s1
Bioactivity Comments
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) [3]. 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 [6]. 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 [2]. An EC50 of ~4.5nM for IFNα production in PBMCs is reported [2].
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
TLR7 Primary target of this compound Hs Agonist Agonist - - - 2