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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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.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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)
InChI Key CJTVDIBZBUWIFC-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
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]