lazucirnon   Click here for help

GtoPdb Ligand ID: 10653

Synonyms: AKST-4290 | AKST4290 | ALK-4290 | ALK4290 | Example 11 [WO2012045803A1]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Lazucirnon (AKST4290, formerly known as ALK4290) is a CCR3 antagonist that was developed by Alkahest as a novel oral therapy for wet age-related macular degeneration (AMD). It acts as a modulator of pathologic inflammation by inhibiting the CCR3/eotaxin axis and subsequent eosinophil accumulation. ALK4290 is now being repurposed for Parkinson's disease. The structure that is presented here was obtained from the NIH ChemIDplus chemical information resource, where it is listed as ALK4290. The structure matches example 11 that is claimed in patent WO2012045803A1 which was granted to Boehringer Ingelheim [2].
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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 8
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 85.85
Molecular weight 511.24
XLogP 2.96
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 O=C([C@H]1CCC(=O)N1C1CCN(CC1)Cc1ccc(c(c1)C)Cl)Nc1nc(C)cc(c1)C(=O)N(C)C
Isomeric SMILES O=C([C@H]1CCC(=O)N1C1CCN(CC1)Cc1ccc(c(c1)C)Cl)Nc1nc(C)cc(c1)C(=O)N(C)C
InChI InChI=1S/C27H34ClN5O3/c1-17-13-19(5-6-22(17)28)16-32-11-9-21(10-12-32)33-23(7-8-25(33)34)26(35)30-24-15-20(14-18(2)29-24)27(36)31(3)4/h5-6,13-15,21,23H,7-12,16H2,1-4H3,(H,29,30,35)/t23-/m1/s1
InChI Key DWKNOLCXIFYNFV-HSZRJFAPSA-N
References
1. Filippone RT, Robinson AM, Jovanovska V, Stavely R, Apostolopoulos V, Bornstein JC, Nurgali K. (2018)
Targeting eotaxin-1 and CCR3 receptor alleviates enteric neuropathy and colonic dysfunction in TNBS-induced colitis in guinea pigs.
Neurogastroenterol Motil, 30 (11): e13391. [PMID:29968270]
2. Frank M, Haerberle H, Henry M, Pachur T, Santagostino M, Stertz U, Trebling T, Werthmann U. (2012)
Co-crystals and salts of ccr3-inhibitors.
Patent number: WO2012045803A1. Assignee: Boehringer Ingelheim International Gmbh. Priority date: 07/10/2010. Publication date: 12/04/2012.
3. Gauvreau GM, FitzGerald JM, Boulet LP, Watson RM, Hui L, Villineuve H, Scime TX, Schlatman AR, Obminski C, Kum J et al.. (2018)
The effects of a CCR3 inhibitor, AXP1275, on allergen-induced airway responses in adults with mild-to-moderate atopic asthma.
Clin Exp Allergy, 48 (4): 445-451. [PMID:29423947]
4. Grozdanovic M, Laffey KG, Abdelkarim H, Hitchinson B, Harijith A, Moon HG, Park GY, Rousslang LK, Masterson JC, Furuta GT et al.. (2019)
Novel peptide nanoparticle-biased antagonist of CCR3 blocks eosinophil recruitment and airway hyperresponsiveness.
J Allergy Clin Immunol, 143 (2): 669-680.e12. [PMID:29778505]
5. Hirahara S, Nozaki M, Ohbayashi M, Hasegawa N, Ozone D, Ogura Y. (2017)
Suppression of Retinal Neovascularization by Anti-CCR3 Treatment in an Oxygen-Induced Retinopathy Model in Mice.
Ophthalmic Res, 58 (1): 56-66. [PMID:28376500]
6. Sui Y, Zhang Y, Dong C, Xu B, Sun X. (2019)
The small molecular CCR3 antagonist YM344031 attenuates neurodegenerative pathologies and improves learning and memory performance in a mouse model of Alzheimer's disease.
Brain Res, 1719: 1-10. [PMID:31121157]
7. Zhu C, Xu B, Sun X, Zhu Q, Sui Y. (2017)
Targeting CCR3 to Reduce Amyloid-β Production, Tau Hyperphosphorylation, and Synaptic Loss in a Mouse Model of Alzheimer's Disease.
Mol Neurobiol, 54 (10): 7964-7978. [PMID:27878757]