5-LOX inhibitor 2m [PMID: 30199704]   Click here for help

GtoPdb Ligand ID: 10079

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 2m is reported as a competitive inhibitor of the 5-lipoxygenase (5-LOX) enzyme. It was developed for anti-inflammatory potential [4]. 2m was the most active inhibtor identified from the thiazole series in this pharmacophore modeling study. The thiazole series of compounds was designed with the aim of reducing the hepatotoxicity that is associated with N-hydroxyurea class 5-LOX inhibitors [3] such as zileuton, atreleuton (ABT-761; PubChem CID 3086671) [1] and MLN-977 (PubChem CID 9905233) [2]. 2m is devoid of radical scavenging activity.
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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 3
Hydrogen bond donors 0
Rotatable bonds 7
Topological polar surface area 70.67
Molecular weight 462.14
XLogP 7.29
No. Lipinski's rules broken 1
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 COc1ccc(cc1)c1nc(sc1C(=O)c1ccccc1)N(c1ccccc1)c1ccccc1
Isomeric SMILES COc1ccc(cc1)c1nc(sc1C(=O)c1ccccc1)N(c1ccccc1)c1ccccc1
InChI InChI=1S/C29H22N2O2S/c1-33-25-19-17-21(18-20-25)26-28(27(32)22-11-5-2-6-12-22)34-29(30-26)31(23-13-7-3-8-14-23)24-15-9-4-10-16-24/h2-20H,1H3
InChI Key GCBYJNQEZBSRJO-UHFFFAOYSA-N
References
1. Brooks CD, Stewart AO, Basha A, Bhatia P, Ratajczyk JD, Martin JG, Craig RA, Kolasa T, Bouska JB, Lanni C et al.. (1995)
(R)-(+)-N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl- 2-propynyl]-N-hydroxyurea (ABT-761), a second-generation 5-lipoxygenase inhibitor.
J Med Chem, 38 (24): 4768-75. [PMID:7490726]
2. Lewis TA, Bayless L, Eckman JB, Ellis JL, Grewal G, Libertine L, Marie Nicolas J, Scannell RT, Wels BF, Wenberg K et al.. (2004)
5-lipoxygenase inhibitors with histamine H(1) receptor antagonist activity.
Bioorg Med Chem Lett, 14 (9): 2265-8. [PMID:15081022]
3. Malec J, Przybyszewski WM, Grabarczyk M, Sitarska E. (1984)
Hydroxyurea has the capacity to induce damage to human erythrocytes which can be modified by radical scavengers.
Biochem Biophys Res Commun, 120 (2): 566-73. [PMID:6732772]
4. Sinha S, Doble M, Manju SL. (2018)
Design, synthesis and identification of novel substituted 2-amino thiazole analogues as potential anti-inflammatory agents targeting 5-lipoxygenase.
Eur J Med Chem, 158: 34-50. [PMID:30199704]