CR4056   Click here for help

GtoPdb Ligand ID: 10453

Synonyms: CR-4056 | US8633208, 1
Compound class: Synthetic organic
Comment: CR4056 is reported to bind imidazoline-binding sites known as imidazoline receptor I2 [2]. It was developed by Rottapharm Biotech and is being pursued as a novel analgesic for inflammatory and neuropathic pain [1,3-4]. Potential for efficacy in humans has been demonstrated in rodent models of nociceptive and neuropathic pain. To date (August 2019) clinical efficacy from a proof-of-concept study in patients with knee osteoarthritis pain has only been reported in meeting abstract form (see Rovati et al. Abstract Number: 1193, 2017 ACR/ARHP Annual Meeting). The associated trial registry number is EudraCT 2015-001136-37.
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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 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 3
Hydrogen bond donors 0
Rotatable bonds 2
Topological polar surface area 43.08
Molecular weight 272.11
XLogP 2.92
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 c1ccc(cc1)c1ncc2c(n1)ccc(c2)n1cncc1
Isomeric SMILES c1ccc(cc1)c1ncc2c(n1)ccc(c2)n1cncc1
InChI InChI=1S/C17H12N4/c1-2-4-13(5-3-1)17-19-11-14-10-15(6-7-16(14)20-17)21-9-8-18-12-21/h1-12H
InChI Key CSZGXYBGYFNSCO-UHFFFAOYSA-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. Ferrari F, Fiorentino S, Mennuni L, Garofalo P, Letari O, Mandelli S, Giordani A, Lanza M, Caselli G. (2011)
Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain.
J Pain Res, 4: 111-25. [PMID:21647215]
2. Li JX. (2017)
Imidazoline I2 receptors: An update.
Pharmacol Ther, 178: 48-56. [PMID:28322973]
3. Siemian JN, Wang K, Zhang Y, Li JX. (2018)
Mechanisms of imidazoline I2 receptor agonist-induced antinociception in rats: involvement of monoaminergic neurotransmission.
Br J Pharmacol, 175 (9): 1519-1534. [PMID:29451703]
4. Thorn DA, Qiu Y, Jia S, Zhang Y, Li JX. (2016)
Antinociceptive effects of imidazoline I2 receptor agonists in the formalin test in rats.
Behav Pharmacol, 27 (4): 377-83. [PMID:26599907]