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gaboxadol   Click here for help

GtoPdb Ligand ID: 4322

Synonyms: LU-02030 | MK-0928 | MK0928 | OV101 | THIP
PDB Ligand
Compound class: Synthetic organic
Comment: GABAA agonist, with some preference for δ subunit-containing channels [6].

gaboxadol is commercially available from our sponsors

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 2
Hydrogen bond donors 2
Rotatable bonds 0
Topological polar surface area 58.03
Molecular weight 140.06
XLogP -0.63
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 O=c1[nH]oc2c1CCNC2
Isomeric SMILES O=c1[nH]oc2c1CCNC2
InChI InChI=1S/C6H8N2O2/c9-6-4-1-2-7-3-5(4)10-8-6/h7H,1-3H2,(H,8,9)
InChI Key ZXRVKCBLGJOCEE-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. Bird LM, Ochoa-Lubinoff C, Tan WH, Heimer G, Melmed RD, Rakhit A, Visootsak J, During MJ, Holcroft C, Burdine RD et al.. (2021)
The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome.
Neurology, 96 (7): e1024-e1035. [PMID:33443117]
2. Braat S, Kooy RF. (2015)
Insights into GABAAergic system deficits in fragile X syndrome lead to clinical trials.
Neuropharmacology, 88: 48-54. [PMID:25016041]
3. Campbell MM, Mickel SJ, Singh G. (1991)
(±)-2-amino-2-thiazoline-4-ethanoic acid; a novel, specific GABAA receptor agonist.
Bioorg Med Chem Lett, 1 (5): 247-148. DOI: 10.1016/S0960-894X(01)81035-0
4. Cogram P, Deacon RMJ, Warner-Schmidt JL, von Schimmelmann MJ, Abrahams BS, During MJ. (2019)
Gaboxadol Normalizes Behavioral Abnormalities in a Mouse Model of Fragile X Syndrome.
Front Behav Neurosci, 13: 141. [PMID:31293404]
5. Copping NA, McTighe SM, Fink KD, Silverman JL. (2021)
Emerging Gene and Small Molecule Therapies for the Neurodevelopmental Disorder Angelman Syndrome.
Neurotherapeutics, 18 (3): 1535-1547. [PMID:34528170]
6. Frølund B, Kristiansen U, Brehm L, Hansen AB, Krogsgaard-Larsen P, Falch E. (1995)
Partial GABAA receptor agonists. Synthesis and in vitro pharmacology of a series of nonannulated analogs of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol.
J Med Chem, 38 (17): 3287-96. [PMID:7650683]
7. Keary C, Bird LM, de Wit MC, Hatti S, Heimer G, Heussler H, Kolevzon A, Mathews A, Ochoa-Lubinoff C, Tan WH et al.. (2023)
Gaboxadol in angelman syndrome: A double-blind, parallel-group, randomized placebo-controlled phase 3 study.
Eur J Paediatr Neurol, 47: 6-12. [PMID:37639777]
8. Krehan D, Frølund B, Ebert B, Nielsen B, Krogsgaard-Larsen P, Johnston GA, Chebib M. (2003)
Aza-THIP and related analogues of THIP as GABA C antagonists.
Bioorg Med Chem, 11 (23): 4891-6. [PMID:14604650]
9. Larsen M, Holm R, Jensen KG, Brodin B, Nielsen CU. (2009)
Intestinal gaboxadol absorption via PAT1 (SLC36A1): modified absorption in vivo following co-administration of L-tryptophan.
Br J Pharmacol, 157 (8): 1380-9. [PMID:19594759]
10. Lozano R, Hare EB, Hagerman RJ. (2014)
Modulation of the GABAergic pathway for the treatment of fragile X syndrome.
Neuropsychiatr Dis Treat, 10: 1769-79. [PMID:25258535]
11. Thwaites DT, Anderson CM. (2011)
The SLC36 family of proton-coupled amino acid transporters and their potential role in drug transport.
Br J Pharmacol, 164 (7): 1802-16. [PMID:21501141]