PZM21   Click here for help

GtoPdb Ligand ID: 9286

Synonyms: (S,S)-1-[2-(dimethylamino)-3-(4-hydroxyphenyl)propyl]-3-(1-thiophen-3-ylpropan-2-yl)urea | (S,S)-21 [PMID: 27533032]
PDB Ligand
Compound class: Synthetic organic
Comment: PZM21 is a potent, selective μ opioid receptor agonist with bias towards G-protein (Gi) activation over β-arrestin 2 recruitment [1]. This provides a compound with reduced propensity to produce common opioid side effects whilst retaining analgesic activity. PZM21 is being used experimentally for its analgesic activity.
This compound is not in PubChem and its SMILES string does not retrieve any patent documents from SureChembl (late August 2016).
Compare this with oliceridine, a chemically unrelated μ opioid receptor G-protein biased agonist.
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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

PZM21 is commercially available from our sponsors

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 4
Hydrogen bond donors 3
Rotatable bonds 10
Topological polar surface area 92.84
Molecular weight 361.18
XLogP 2.42
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 CC(Cc1cscc1)NC(=O)NCC(N(C)C)Cc1ccc(cc1)O
Isomeric SMILES C[C@@H](Cc1cscc1)NC(=O)NC[C@@H](N(C)C)Cc1ccc(cc1)O
InChI InChI=1S/C19H27N3O2S/c1-14(10-16-8-9-25-13-16)21-19(24)20-12-17(22(2)3)11-15-4-6-18(23)7-5-15/h4-9,13-14,17,23H,10-12H2,1-3H3,(H2,20,21,24)/t14-,17-/m0/s1
InChI Key MEDBIJOVZJEMBI-YOEHRIQHSA-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/)
Bioactivity Comments
In mouse experiments PZM21 produces significant analgesia but with markedly reduced side effects of constipation and respiratory depression compared to morphine [1].

PZM21 is selective for the μ opiod receptor over other GPCRs tested, and does not inhibit neurotransmitter transporters with high affinity [1]. It behaves as an antagonist of the κ opiod receptor (Ki 18nM). PZM21 inhibits hERG with IC50 2000-4000nM.
Selectivity at GPCRs
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
μ receptor Primary target of this compound Hs Agonist Biased agonist 9.0 pKi - 1
⤷ pKi 9.0 (Ki 1.1x10-9 M) [1]
μ receptor Primary target of this compound Hs Agonist Biased agonist 8.3 pEC50 - 1
⤷ pEC50 8.3 (EC50 4.6x10-9 M) [1]
Description: In a Gi/o activation assay.