ABX-1431   Click here for help

GtoPdb Ligand ID: 10062

Synonyms: ABX1431 | compound 28 [PMID: 30067909] | compound 9aq [WO2013103973A1] | example 82 [WO2013103973A1]
Compound class: Synthetic organic
Comment: ABX-1431 is a potent, orally available, and selective covalent (irreversible) inhibitor of monoacylglycerol lipase (MGLL) [2]. It is one of the chemical structures that are claimed in patent WO2013103973A1 [1]. MGLL inhibition increases the level of the endogenous cannabinoid receptor agonist 2-arachidonoylglycerol (2-AG) and CB1 receptor signalling in the central nervous system, and reduces arachidonic acid and eicosanoid levels to better regulate neurotransmission. Modulation of these neurotransmitter molecules induces antinociceptive, anxiolytic, and antineuroinflammatory effects, but is devoid of the psychoactive effects that would be produced by direct cannabinoid receptor activation. Target engagement by ABX-1431 in the brain has been confirmed in a PET occupancy study [1].
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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 5
Hydrogen bond donors 0
Rotatable bonds 9
Topological polar surface area 36.02
Molecular weight 507.16
XLogP 6.02
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 O=C(N1CCN(CC1)Cc1ccc(cc1N1CCCC1)C(F)(F)F)OC(C(F)(F)F)C(F)(F)F
Isomeric SMILES O=C(N1CCN(CC1)Cc1ccc(cc1N1CCCC1)C(F)(F)F)OC(C(F)(F)F)C(F)(F)F
InChI InChI=1S/C20H22F9N3O2/c21-18(22,23)14-4-3-13(15(11-14)31-5-1-2-6-31)12-30-7-9-32(10-8-30)17(33)34-16(19(24,25)26)20(27,28)29/h3-4,11,16H,1-2,5-10,12H2
InChI Key SQZJGTOZFRNWCX-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/)
No information available.
Summary of Clinical Use Click here for help
ABX-1431 has advanced to Phase 2 clinical trial. A study designed to evaluate its clinical efficacy in patients with Tourette syndrome or chronic motor tic disorder is planned (see NCT03625453). Phase 1 studies to determine efficacy in abrogating central pain are ongoing (e.g. NCT03138421).
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03138421 Central Pain Study for ABX-1431 Phase 1 Interventional Abide Therapeutics
NCT03625453 Study of ABX-1431 in Adult Patients With Tourette Syndrome or Chronic Motor Tic Disorder Phase 2 Interventional Abide Therapeutics