compound 16 [PMID: 31498617]   Click here for help

GtoPdb Ligand ID: 10482

PDB Ligand
Compound class: Synthetic organic
Comment: Compound 16 is reported as a novel, selective agonist of the class A orphan GPCR, MRGPRX1 [1]. Compound 16 is extensively metabolised in mouse liver microsomes and this probably accounts for the short in vivo half-life (~20 m in) that was observed following intravenous administration in mice.
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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 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.

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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 111.92
Molecular weight 435.13
XLogP 4.47
No. Lipinski's rules broken 0
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.

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Canonical SMILES COc1ccccc1S(=O)(=O)Nc1ccc(cc1Oc1ccc2c(c1)ccnc2N)C
Isomeric SMILES COc1ccccc1S(=O)(=O)Nc1ccc(cc1Oc1ccc2c(c1)ccnc2N)C
InChI InChI=1S/C23H21N3O4S/c1-15-7-10-19(26-31(27,28)22-6-4-3-5-20(22)29-2)21(13-15)30-17-8-9-18-16(14-17)11-12-25-23(18)24/h3-14,26H,1-2H3,(H2,24,25)
InChI Key BWEJNHRMGZUMNU-UHFFFAOYSA-N
Bioactivity Comments
Compound 16 is selective for MRGPRX1 compared to opioid receptors [1]. It does not exhibit agonist activity at mouse MrgprC11. Since mice lack a MRGPRX1 orthologous receptor, experiments to evaluate the effects of compound 16 in humanized MrgprX1 mice are underway.
Selectivity at GPCRs
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
δ receptor Hs None Binding 5.6 pKi - 1
⤷ pKi 5.6 (Ki 2.47x10-6 M) [1]
Description: Receptor binding in a radioligand displacement assay using [3H]DADLE as tracer.
μ receptor Hs None Binding 5.4 pKi - 1
⤷ pKi 5.4 (Ki 3.73x10-6 M) [1]
Description: Receptor binding in a radioligand displacement assay using [3H]DAMGO as tracer.
κ receptor Hs None Binding 4.9 pKi - 1
⤷ pKi 4.9 (Ki 1.21x10-5 M) [1]
Description: Receptor binding in a radioligand displacement assay using [3H]U-69,593 as tracer.
MRGPRX1 Hs Agonist Agonist 7.3 pEC50 - 1
⤷ pEC50 7.3 (EC50 5x10-8 M) [1]
Description: Agonist activity at human MRGPRX1 stably expressed in HEK293 cells by FLIPR claciun mobilisation assay.