compound 16 [PMID: 31498617]   

GtoPdb Ligand ID: 10482

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.
2D Structure
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Physico-chemical Properties
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
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.