Spaglumic acid

Identification

Summary

Spaglumic acid is the β-aspartyl isoform of N-Acetyl-l-aspartylglutamate, a naturally occurring neurotransmitter, used in allergic eye conditions due to its ability to stabilize mast cells.

Generic Name
Spaglumic acid
DrugBank Accession Number
DB08835
Background

Spaglumic acid is the β-aspartyl isoform of N-Acetyl-l-aspartylglutamate (isospaglumic Acid is N-(N-Acetyl-l-α-aspartyl)-l-glutamic acid). In eye drops, spaglumic acid is either a magnesium or sodium salt of N-Acetyl-l-aspartylglutamate. Spaglumic acid is a mast cell stabilizer. Thus it is used in allergic conditions such as allergic conjunctivitis. Specifically spaglumic acid is approved in Portugal under the brand name Naabak and in Greece under the brand name Naaxia for use in patients with allergic conjunctivitis.

Type
Small Molecule
Groups
Experimental
Structure
Weight
Average: 304.255
Monoisotopic: 304.090665483
Chemical Formula
C11H16N2O8
Synonyms
  • N-Acetyl-L-β-aspartyl-L-glutamic acid
  • Spaglumic acid

Pharmacology

Indication

Used in patients with allergic conjunctivitis.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofOcular inflammation•••••••••••••••••••• • •••••
Treatment ofOcular inflammation•••••••••••••••••••• • •••••
Treatment ofOcular inflammation•••••••••••••••••••• • •••••
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Pharmacodynamics

Not Available

Mechanism of action

Spaglumic acid is a mast cell stabilizer. Mast cells are involved in producing an allergic response by releasing inflammatory mediators such as histamine. Mast cell stablizers block the release of histamine and other mediators by inhibiting mast cell degranulation, which is the process of releasing these mediators. Inhibition occurs through inhibition of specific calcium channels to stabilize the mast cell and prevent degranulation.

TargetActionsOrganism
UGlutamate carboxypeptidase 2
ligand
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
  • Take with or without food.

Products

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International/Other Brands
Naabak (Thea)

Categories

ATC Codes
R01AC05 — Spaglumic acidS01GX03 — Spaglumic acid
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as hybrid peptides. These are compounds containing at least two different types of amino acids (alpha, beta, gamma, delta) linked to each other through a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Hybrid peptides
Direct Parent
Hybrid peptides
Alternative Parents
Glutamic acid and derivatives / Asparagine and derivatives / N-acyl-L-alpha-amino acids / Tricarboxylic acids and derivatives / N-acyl amines / Acetamides / Secondary carboxylic acid amides / Carboxylic acids / Organopnictogen compounds / Organonitrogen compounds
show 3 more
Substituents
Acetamide / Aliphatic acyclic compound / Alpha-amino acid or derivatives / Asparagine or derivatives / Carbonyl group / Carboxamide group / Carboxylic acid / Carboxylic acid derivative / Fatty acyl / Fatty amide
show 15 more
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
X81L78B3RB
CAS number
4910-46-7
InChI Key
GUCKKCMJTSNWCU-BQBZGAKWSA-N
InChI
InChI=1S/C11H16N2O8/c1-5(14)12-7(11(20)21)4-8(15)13-6(10(18)19)2-3-9(16)17/h6-7H,2-4H2,1H3,(H,12,14)(H,13,15)(H,16,17)(H,18,19)(H,20,21)/t6-,7-/m0/s1
IUPAC Name
(2S)-2-[(3S)-3-carboxy-3-acetamidopropanamido]pentanedioic acid
SMILES
CC(=O)N[C@@H](CC(=O)N[C@@H](CCC(O)=O)C(O)=O)C(O)=O

References

Synthesis Reference

Reddy AV, Ravindranath B: Synthesis of alpha-, beta- and cyclic spaglumic acids. Int J Pept Protein Res. 1992 Nov;40(5):472-6.

General References
  1. Sala-Rabanal M, Loo DD, Hirayama BA, Turk E, Wright EM: Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1. J Physiol. 2006 Jul 1;574(Pt 1):149-66. Epub 2006 Apr 20. [Article]
  2. Sanchis-Merino ME, Montero JA, Ruiz-Moreno JM, Rodriguez AE, Pastor S: Comparative efficacy of topical antihistamines in an animal model of early phase allergic conjunctivitis. Exp Eye Res. 2008 May;86(5):791-7. doi: 10.1016/j.exer.2008.02.007. Epub 2008 Mar 4. [Article]
  3. Purello D'Ambrosio F, Gangemi S, Ricciardi L, Cuzzocrea S, Di Lorenzo G: Lodoxamide versus spaglumic acid: a comparative double-blind trial on patients suffering from seasonal allergic conjunctivitis induced by Parietaria pollen. Allergol Immunopathol (Madr). 1997 Sep-Oct;25(5):233-7. [Article]
KEGG Drug
D07374
PubChem Compound
210320
PubChem Substance
175427113
ChemSpider
182277
ChEBI
135289
ChEMBL
CHEMBL2105616
ZINC
ZINC000002504638
Drugs.com
Drugs.com Drug Page
Wikipedia
N-Acetylaspartylglutamic_acid
MSDS
Download (37.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAllergic Conjunctivitis (AC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
SolutionOphthalmic4.9 %
Solution / dropsOphthalmic
Solution / dropsOphthalmic49 MG/ML
SolutionOphthalmic4.9 g/100ml
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility3.22 mg/mLALOGPS
logP-1ALOGPS
logP-2.3Chemaxon
logS-2ALOGPS
pKa (Strongest Acidic)3.01Chemaxon
pKa (Strongest Basic)-2Chemaxon
Physiological Charge-3Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count5Chemaxon
Polar Surface Area170.1 Å2Chemaxon
Rotatable Bond Count9Chemaxon
Refractivity64.06 m3·mol-1Chemaxon
Polarizability27.37 Å3Chemaxon
Number of Rings0Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.8688
Blood Brain Barrier+0.7025
Caco-2 permeable-0.8358
P-glycoprotein substrateNon-substrate0.7019
P-glycoprotein inhibitor INon-inhibitor0.8938
P-glycoprotein inhibitor IINon-inhibitor0.9265
Renal organic cation transporterNon-inhibitor0.9589
CYP450 2C9 substrateNon-substrate0.7215
CYP450 2D6 substrateNon-substrate0.8409
CYP450 3A4 substrateNon-substrate0.6367
CYP450 1A2 substrateNon-inhibitor0.9339
CYP450 2C9 inhibitorNon-inhibitor0.9386
CYP450 2D6 inhibitorNon-inhibitor0.9636
CYP450 2C19 inhibitorNon-inhibitor0.9666
CYP450 3A4 inhibitorNon-inhibitor0.9201
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9817
Ames testNon AMES toxic0.7179
CarcinogenicityNon-carcinogens0.9381
BiodegradationReady biodegradable0.8507
Rat acute toxicity1.7395 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9888
hERG inhibition (predictor II)Non-inhibitor0.9644
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-06rb-0891000000-218620ca674b8145ee6a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0890000000-98cc2cfa8c57b62bbea0
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0910000000-b1ff6e899b9821160ee8
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0007-0910000000-51b4b33020b6f64c38e0
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-4900000000-2c18199f4113a28911c1
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001l-9600000000-886b5539ddf30fa41928
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-176.0104257
predicted
DarkChem Lite v0.1.0
[M-H]-163.88947
predicted
DeepCCS 1.0 (2019)
[M+H]+176.0257257
predicted
DarkChem Lite v0.1.0
[M+H]+166.24747
predicted
DeepCCS 1.0 (2019)
[M+Na]+176.4779257
predicted
DarkChem Lite v0.1.0
[M+Na]+173.41151
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Ligand
General Function
Tetrahydrofolyl-poly(glutamate) polymer binding
Specific Function
Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of fola...
Gene Name
FOLH1
Uniprot ID
Q04609
Uniprot Name
Glutamate carboxypeptidase 2
Molecular Weight
84330.015 Da
References
  1. Bandari RP, Jiang Z, Reynolds TS, Bernskoetter NE, Szczodroski AF, Bassuner KJ, Kirkpatrick DL, Rold TL, Sieckman GL, Hoffman TJ, Connors JP, Smith CJ: Synthesis and biological evaluation of copper-64 radiolabeled [DUPA-6-Ahx-(NODAGA)-5-Ava-BBN(7-14)NH2], a novel bivalent targeting vector having affinity for two distinct biomarkers (GRPr/PSMA) of prostate cancer. Nucl Med Biol. 2014 Apr;41(4):355-63. doi: 10.1016/j.nucmedbio.2014.01.001. Epub 2014 Jan 10. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Other
General Function
L-proline transmembrane transporter activity
Specific Function
Neutral amino acid/proton symporter. Has a pH-dependent electrogenic transport activity for small amino acids such as glycine, alanine and proline. Besides small apolar L-amino acids, it also recog...
Gene Name
SLC36A1
Uniprot ID
Q7Z2H8
Uniprot Name
Proton-coupled amino acid transporter 1
Molecular Weight
53075.045 Da
References
  1. Sala-Rabanal M, Loo DD, Hirayama BA, Turk E, Wright EM: Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1. J Physiol. 2006 Jul 1;574(Pt 1):149-66. Epub 2006 Apr 20. [Article]

Drug created at February 19, 2013 23:31 / Updated at June 12, 2021 10:53