nalfurafine   Click here for help

GtoPdb Ligand ID: 1651

Synonyms: TRK 820 | TRK820
Approved drug PDB Ligand
nalfurafine is an approved drug (Japan (2009))
Compound class: Synthetic organic
Comment: Nalfurafine is a potent κ-opioid receptor OPRK1 agonist [2-3]. OPRK1 activation in spinal neurons suppresses itch transmission in the spinal cord [4].
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 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.

✖
Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 86.38
Molecular weight 476.23
XLogP 1.52
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
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.

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/)

✖
Canonical SMILES CN(C1CCC2(C34C1Oc1c4c(CC2N(CC3)CC2CC2)ccc1O)O)C(=O)C=Cc1ccoc1
Isomeric SMILES CN([C@@H]1CC[C@@]2([C@@]34[C@H]1Oc1c4c(C[C@H]2N(CC3)CC2CC2)ccc1O)O)C(=O)/C=C/c1ccoc1
InChI InChI=1S/C28H32N2O5/c1-29(23(32)7-4-18-9-13-34-16-18)20-8-10-28(33)22-14-19-5-6-21(31)25-24(19)27(28,26(20)35-25)11-12-30(22)15-17-2-3-17/h4-7,9,13,16-17,20,22,26,31,33H,2-3,8,10-12,14-15H2,1H3/b7-4+/t20-,22-,26+,27+,28-/m1/s1
InChI Key XGZZHZMWIXFATA-UEZBDDGYSA-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/)
References
1. Hercz D, Jiang SH, Webster AC. (2020)
Interventions for itch in people with advanced chronic kidney disease.
Cochrane Database Syst Rev, 12: CD011393. [PMID:33283264]
2. Nagase H, Hayakawa J, Kawamura K, Kawai K, Takezawa Y, Matsuura H, Tajima C, Endo T. (1998)
Discovery of a structurally novel opioid kappa-agonist derived from 4,5-epoxymorphinan.
Chem Pharm Bull (Tokyo), 46 (2): 366-9. [PMID:9501472]
3. Seki T, Awamura S, Kimura C, Ide S, Sakano K, Minami M, Nagase H, Satoh M. (1999)
Pharmacological properties of TRK-820 on cloned mu-, delta- and kappa-opioid receptors and nociceptin receptor.
Eur J Pharmacol, 376 (1-2): 159-67. [PMID:10440101]
4. Sheahan TD, Warwick CA, Cui AY, Baranger DAA, Perry VJ, Smith KM, Manalo AP, Nguyen EK, Koerber HR, Ross SE. (2024)
Kappa opioids inhibit spinal output neurons to suppress itch.
Sci Adv, 10 (39): eadp6038. [PMID:39321286]
5. Wang Y, Tang K, Inan S, Siebert D, Holzgrabe U, Lee DY, Huang P, Li JG, Cowan A, Liu-Chen LY. (2005)
Comparison of pharmacological activities of three distinct kappa ligands (Salvinorin A, TRK-820 and 3FLB) on kappa opioid receptors in vitro and their antipruritic and antinociceptive activities in vivo.
J Pharmacol Exp Ther, 312 (1): 220-30. [PMID:15383632]