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)
1. Bekerman E, Neveu G, Shulla A, Brannan J, Pu SY, Wang S, Xiao F, Barouch-Bentov R, Bakken RR, Mateo R et al.. (2017)
Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects.
J Clin Invest, 127 (4): 1338-1352. [PMID:28240606]
2. Neveu G, Barouch-Bentov R, Ziv-Av A, Gerber D, Jacob Y, Einav S. (2012)
Identification and targeting of an interaction between a tyrosine motif within hepatitis C virus core protein and AP2M1 essential for viral assembly.
PLoS Pathog, 8 (8): e1002845. [PMID:22916011]
3. Neveu G, Ziv-Av A, Barouch-Bentov R, Berkerman E, Mulholland J, Einav S. (2015)
AP-2-associated protein kinase 1 and cyclin G-associated kinase regulate hepatitis C virus entry and are potential drug targets.
J Virol, 89 (8): 4387-404. [PMID:25653444]
4. Verdonck S, Pu SY, Sorrell FJ, Elkins JM, Froeyen M, Gao LJ, Prugar LI, Dorosky DE, Brannan JM, Barouch-Bentov R et al.. (2019)
Synthesis and Structure-Activity Relationships of 3,5-Disubstituted-pyrrolo[2,3- b]pyridines as Inhibitors of Adaptor-Associated Kinase 1 with Antiviral Activity.
J Med Chem, 62 (12): 5810-5831. [PMID:31136173]