compound 21b [PMID: 31136173]   Click here for help

GtoPdb Ligand ID: 10403

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 21b is reported as a non-selective inhibitor of AP2 associated kinase 1 (AAK1) [4], a kinase that is involved in protein trafficking in endocytic membranes via regulation of subunits within the AP2 adaptor complex. The host AP2 complex is expoited by viruses to enable host cell infection and viral assembly [2]. Host AAK1 is required for the life cycles of Flaviviridae family viruses, including the Dengue and Ebola viruses [1-3], making AAK1 a potential drug target for the development of broad-spectrun anti-viral agents [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 2
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 60.03
Molecular weight 355.13
XLogP 4.42
No. Lipinski's rules broken 0
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Canonical SMILES COc1cc(ccc1OC)c1cnc2c(c1)c(C#Cc1cccnc1)c[nH]2
Isomeric SMILES COc1cc(ccc1OC)c1cnc2c(c1)c(C#Cc1cccnc1)c[nH]2
InChI InChI=1S/C22H17N3O2/c1-26-20-8-7-16(11-21(20)27-2)18-10-19-17(13-24-22(19)25-14-18)6-5-15-4-3-9-23-12-15/h3-4,7-14H,1-2H3,(H,24,25)
Bioactivity Comments
Results from a KINOMEScan® selectivity screen highlight that compound 21b cannot be considered as a selective AAK1 inhibitor. It targets multiple other kinases that could contribute to its antiviral activity. Compound 21b does however, have an improved selectivity profile compared to sunitinib (an approved anticancer drug), which also inhibits AAK1 and has reported antiviral activity [3].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
AP2 associated kinase 1 Hs Inhibitor Inhibition 8.4 pIC50 - 4
pIC50 8.4 (IC50 4x10-9 M) [4]
Description: Inhibition of kinase activity in a LanthaScreen® assay.