LX2931   Click here for help

GtoPdb Ligand ID: 9851

Synonyms: LX3305
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: LX2931 (LX3305) is a first-in-class, orally available, functional S1P lyase inhibitor, that has been investigated for anti-inflammatory potential [1]. Note that LX2931 does not block S1PL catalytic activity in a biochemical assay even at 100 μM [6].
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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 4
Hydrogen bond donors 6
Rotatable bonds 5
Topological polar surface area 110.35
Molecular weight 245.1
XLogP 0.33
No. Lipinski's rules broken 1

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(=c1[nH]c(c[nH]1)C(C(C(CO)O)O)O)N=O
Isomeric SMILES C/C(=c/1\[nH]c(c[nH]1)[C@H]([C@@H]([C@@H](CO)O)O)O)/N=O
InChI InChI=1S/C9H15N3O5/c1-4(12-17)9-10-2-5(11-9)7(15)8(16)6(14)3-13/h2,6-8,10-11,13-16H,3H2,1H3/b9-4+/t6-,7-,8-/m1/s1
InChI Key CGJLPLVZAAEKTK-LIVYHJONSA-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. Bagdanoff JT, Donoviel MS, Nouraldeen A, Carlsen M, Jessop TC, Tarver J, Aleem S, Dong L, Zhang H, Boteju L et al.. (2010)
Inhibition of sphingosine 1-phosphate lyase for the treatment of rheumatoid arthritis: discovery of (E)-1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone oxime (LX2931) and (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol (LX2932).
J Med Chem, 53 (24): 8650-62. [PMID:21090716]
2. Bagdanoff JT, Donoviel MS, Nouraldeen A, Tarver J, Fu Q, Carlsen M, Jessop TC, Zhang H, Hazelwood J, Nguyen H et al.. (2009)
Inhibition of sphingosine-1-phosphate lyase for the treatment of autoimmune disorders.
J Med Chem, 52 (13): 3941-53. [PMID:19489538]
3. Billich A, Beerli C, Bergmann R, Bruns C, Loetscher E. (2013)
Cellular assay for the characterization of sphingosine-1-phosphate lyase inhibitors.
Anal Biochem, 434 (2): 247-53. [PMID:23246729]
4. Loetscher E, Schneider K, Beerli C, Billich A. (2013)
Assay to measure the secretion of sphingosine-1-phosphate from cells induced by S1P lyase inhibitors.
Biochem Biophys Res Commun, 433 (3): 345-8. [PMID:23499842]
5. Schwab SR, Pereira JP, Matloubian M, Xu Y, Huang Y, Cyster JG. (2005)
Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients.
Science, 309 (5741): 1735-9. [PMID:16151014]
6. Weiler S, Braendlin N, Beerli C, Bergsdorf C, Schubart A, Srinivas H, Oberhauser B, Billich A. (2014)
Orally active 7-substituted (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as active-site inhibitors of sphingosine 1-phosphate lyase for the treatment of multiple sclerosis.
J Med Chem, 57 (12): 5074-84. [PMID:24809814]
7. Yu XQ, Kramer J, Moran L, O'Neill E, Nouraldeen A, Oravecz T, Wilson AG. (2010)
Pharmacokinetic/pharmacodynamic modelling of 2-acetyl-4(5)-tetrahydroxybutyl imidazole-induced peripheral lymphocyte sequestration through increasing lymphoid sphingosine 1-phosphate.
Xenobiotica, 40 (5): 350-6. [PMID:20175664]