compound 17 [PMID: 36111834]   Click here for help

GtoPdb Ligand ID: 12185

Compound class: Synthetic organic
Comment: This is a small molecule that can be used to examine the effects of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) inhibition on the viral lifecycle [1]. Compound 17 is selective for PIKfyve, and it has been demonstrated to disrupt both entry and replication of β-coronaviruses in vitro. Its core structure was derived from the non-selective kinase inhibitor AMG28.
Click here for help

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.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. 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.

✖
Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 1
Topological polar surface area 70.83
Molecular weight 331.18
XLogP 2.73
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

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.

✖
Canonical SMILES CN(CC#Cc1ccc2c(c1)c1c([nH]2)CCCc2c1nc(N)nc2)C
Isomeric SMILES Nc1ncc2CCCc3c(c2n1)c1c([nH]3)ccc(c1)C#CCN(C)C
InChI InChI=1S/C20H21N5/c1-25(2)10-4-5-13-8-9-16-15(11-13)18-17(23-16)7-3-6-14-12-22-20(21)24-19(14)18/h8-9,11-12,23H,3,6-7,10H2,1-2H3,(H2,21,22,24)
InChI Key DORZPJWJOBMQKC-UHFFFAOYSA-N
Bioactivity Comments
Compound 17 inhibits SARS-CoV-2 replication in a luciferase-based assay using human epithelial A549-ACE2 cells (IC50 19.5 nM; in the same replication assay remdesivir gave an IC50 of 86 nM), and reduces uptake of His6-SARS-CoV-2 spike protein by HEK293T-ACE2, Calu-3, and Caco-2 cells [1].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
phosphoinositide kinase, FYVE-type zinc finger containing Hs Inhibitor Inhibition 8.2 – 8.4 pIC50 - 1
⤷ pIC50 8.4 (IC50 4.01x10-9 M) [1]
Description: Determined in a cell-based NanoBRET assay
pIC50 8.2 (IC50 6.9x10-9 M) [1]
Description: Inhibition of hPIKFYVE in a proprietary ADP-Glo enzymatic assay
myosin light chain kinase family member 4 Hs Inhibitor Inhibition 6.6 pIC50 - 1
⤷ pIC50 6.6 (IC50 2.65x10-7 M) [1]
Description: Determined in a cell-based NanoBRET assay