LUF7244   Click here for help

GtoPdb Ligand ID: 10447

Synonyms: compound 7i [PMID: 26519929]
Compound class: Synthetic organic
Comment: LUF7244 is a negative allosteric modulator (NAM) of orthosteric ligand binding to the hERG channel (Kv11.1) [2]. It was used to test the hypothesis that hERG NAMs might be able to counteract the proarrhythmic effects of hERG-blocking drugs. Using dofetilide as a known hERG orthosteric channel blocker, LUF7244 has been shown to protect against dofetilide‐induced early after depolarizations (EADs) in vitro and dofetilide‐induced TdP arrhythmia in vivo [1]. It has been proposed that hERG NAMs might find therapeutic potential to alleviate long QTs caused by hERG-blocking drugs, and/or to treat patients with congential long QT syndromes that are associated with Kv11.1 and Kv7.1 channels.
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 1
Rotatable bonds 7
Topological polar surface area 68.29
Molecular weight 366.08
XLogP 3.6
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 O=C(Nc1cccnc1)COc1ccc(cc1)C(=O)c1cccc(c1)Cl
Isomeric SMILES O=C(Nc1cccnc1)COc1ccc(cc1)C(=O)c1cccc(c1)Cl
InChI InChI=1S/C20H15ClN2O3/c21-16-4-1-3-15(11-16)20(25)14-6-8-18(9-7-14)26-13-19(24)23-17-5-2-10-22-12-17/h1-12H,13H2,(H,23,24)
InChI Key KKKJYDOHVKIIQP-UHFFFAOYSA-N
Bioactivity Comments
LUF7244 significantly increases the dissociation of [3H]dofetilide from the Kv11.1 channel, which indicates that it is behaving as a negative allosteric modulator of dofetilide binding to the channel [2].
Selectivity at ion channels
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Kv11.1 Hs Allosteric modulator Negative 5.4 pIC50 - 2
⤷ pIC50 5.4 (IC50 3.9x10-6 M) [2]
Description: Measuring LUF7244-induced reduction in [3H]dofetilide binding to the hKv11.1 channel in vitro.