Oxogluric acid

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Oxogluric acid
Accession Number
DB08845  (DB02926, DB03806, EXPT00137)
Type
Small Molecule
Groups
Experimental, Investigational, Nutraceutical
Description

Oxogluric acid (α-Ketoglutarate) is not approved for any indication in the world but is an investigational drug in the United States. In the United States a phase I clinical trial is investigating whether oxogluric acid precursors found in nutritional supplements can benefit patients with the metabolic disorder propionic acidemia. Oxogluric acid is sold as a dietary supplement to athletes to improve their performance by helping to remove excess ammonia, but it is not officially approved for this indication and only experimental studies have shown a reduction in ammonia by oxogluric acid in hemodialysis patients. Physiologically, oxogluric acid acts in the Krebs cycle as an intermediate, is involved in transamination reactions during the metabolism of amino acids, forms glutamic acid by combining with ammonia, and reduces nitrogen by combining with it as well. Several experimental studies have also shown that administration of oxogluric acid helped attenuate the decreased synthesis of muscle protein that is often seen post-surgery.

Structure
Thumb
Synonyms
  • 2-Ketoglutaric acid
  • 2-Oxo-Glutaric Acid
  • 2-oxoglutaric acid
  • 2-oxopentanedioic acid
  • alfa-ketoglutaric acid
  • alpha-Ketoglutaric acid
  • Ketoglutaric acid
  • Oxoglurate
  • α-Ketoglutarate
External IDs
NSC-17391
Categories
UNII
8ID597Z82X
CAS number
328-50-7
Weight
Average: 146.0981
Monoisotopic: 146.021523302
Chemical Formula
C5H6O5
InChI Key
KPGXRSRHYNQIFN-UHFFFAOYSA-N
InChI
InChI=1S/C5H6O5/c6-3(5(9)10)1-2-4(7)8/h1-2H2,(H,7,8)(H,9,10)
IUPAC Name
2-oxopentanedioic acid
SMILES
OC(=O)CCC(=O)C(O)=O

Pharmacology

Indication

α-α-Ketoglutarate is not approved for any indication in the world but is an investigational drug in the United States. The potential indications for α-Ketoglutarate are in patients with the metabolic disorder propionic acidemia and in trauma patients with muscle loss.

Structured Indications
Not Available
Pharmacodynamics

All of the physiological roles of alpha-ketoglutarate have not been determined. What is known is that alpha-keotglutarate is involved in the Krebs cycle, transamination reactions, and promotes muscle synthesis.

Mechanism of action

The exact mechanisms of action for α-Ketoglutarate have not yet been elucidated. Some of α-Ketoglutarate’s actions include acting in the Krebs cycle as an intermediate, transamination reactions during the metabolism of amino acids, forming glutamic acid by combining with ammonia, and reducing nitrogen by combining with it as well. Concerning α-Ketoglutarate’s actions with ammonia, it is proposed that α-Ketoglutarate can help patients with propionic academia who have high levels of ammonia and low levels of glutamine/glutamate in their blood. Because endogenous glutamate/glutamine is produced from α-Ketoglutarate, propionic acidemia patients have impaired production of α-Ketoglutarate and supplementation of α-Ketoglutarate should improve the condition of these patients. Several other experimental studies have also shown that administration of α-Ketoglutarate in parenteral nutrition given to post-operative patients helped attenuate the decreased synthesis of muscle protein that is often seen after a surgery. This decreased muscle synthesis is speculated to be due to too low α-Ketoglutarate levels.

TargetActionsOrganism
UAspartate aminotransferaseNot AvailableEscherichia coli (strain K12)
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Tanaka, Katsunobu; kimura, Kazu; Yamaguchi, Ken. Fermentative production of a-oxoglutaric acid. U.S. (1973), 4 pp.

General References
  1. Wernerman J, Hammarqvist F, Vinnars E: Alpha-ketoglutarate and postoperative muscle catabolism. Lancet. 1990 Mar 24;335(8691):701-3. [PubMed:1969067]
  2. Allen, Loyd V., Jr. (2012). Remington : The Science and Practice of Pharmacy (22nd ed.). Pharmaceutical Press. [ISBN:978-0857110626]
External Links
Human Metabolome Database
HMDB00208
KEGG Compound
C00026
ChemSpider
50
BindingDB
50303766
ChEBI
30915
ChEMBL
CHEMBL1686
HET
AKG
Wikipedia
Alpha-Ketoglutaric_acid
PDB Entries
1aib / 1bl5 / 1cw4 / 1drt / 1dry / 1ds1 / 1e5i / 1ea0 / 1gp4 / 1gp5
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MSDS
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Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)114 °C (237 °F)From MSDS.
water solubility100 g/l at 20 °C (68 °F)From MSDS.
Predicted Properties
PropertyValueSource
Water Solubility53.1 mg/mLALOGPS
logP-0.6ALOGPS
logP-0.11ChemAxon
logS-0.44ALOGPS
pKa (Strongest Acidic)2.66ChemAxon
pKa (Strongest Basic)-9.7ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area91.67 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity28.88 m3·mol-1ChemAxon
Polarizability12.17 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5552
Blood Brain Barrier+0.8548
Caco-2 permeable-0.7596
P-glycoprotein substrateNon-substrate0.7148
P-glycoprotein inhibitor INon-inhibitor0.9645
P-glycoprotein inhibitor IINon-inhibitor0.8463
Renal organic cation transporterNon-inhibitor0.936
CYP450 2C9 substrateNon-substrate0.8498
CYP450 2D6 substrateNon-substrate0.9016
CYP450 3A4 substrateNon-substrate0.7087
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9612
CYP450 2D6 inhibitorNon-inhibitor0.9707
CYP450 2C19 inhibitorNon-inhibitor0.9708
CYP450 3A4 inhibitorNon-inhibitor0.9749
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9894
Ames testNon AMES toxic0.8752
CarcinogenicityNon-carcinogens0.8462
BiodegradationReady biodegradable0.9535
Rat acute toxicity1.3416 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9774
hERG inhibition (predictor II)Non-inhibitor0.9541
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
GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)GC-MSsplash10-000b-3910000000-4097b7eb52c2910a4277
GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)GC-MSsplash10-0002-1910000000-3277227b9c4da4baa1f7
GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS; 1 MEOX)GC-MSsplash10-00di-9300000000-974bce546caa4fbe6b0f
GC-MS Spectrum - GC-MS (1 MEOX; 2 TMS)GC-MSsplash10-000i-9710000000-d0aea11e947b042571f9
GC-MS Spectrum - GC-MS (1 MEOX; 2 TMS)GC-MSsplash10-052s-4920000000-bf7ed92c68fd4c8dbb6b
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-000b-3910000000-4097b7eb52c2910a4277
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0002-1910000000-3277227b9c4da4baa1f7
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-00di-9300000000-974bce546caa4fbe6b0f
GC-MS Spectrum - GC-MSGC-MSsplash10-000i-9710000000-d0aea11e947b042571f9
GC-MS Spectrum - GC-MSGC-MSsplash10-052s-4920000000-bf7ed92c68fd4c8dbb6b
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-000b-2900000000-e514f7afea2490bbe9ed
Mass Spectrum (Electron Ionization)MSsplash10-0fba-9200000000-4e367c66e94c51eb1a1b
MS/MS Spectrum - Quattro_QQQ 10V, NegativeLC-MS/MSsplash10-0zfr-6900000000-7fc343a243ce5d2a4f39
MS/MS Spectrum - Quattro_QQQ 25V, NegativeLC-MS/MSsplash10-0a4i-9200000000-1a7af9946604baa8b3d2
MS/MS Spectrum - Quattro_QQQ 40V, NegativeLC-MS/MSsplash10-0a4l-9800000000-30495b2afdd3526854e7
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-0002-0925200000-af33449c9638276466c2
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-0a4i-9000000000-6e43f767847790112b65
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-03di-0900000000-4cacc41705b7b385e91e
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-0udi-0900000000-1367eeeb6ad64c67a0aa
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-000t-0915051100-91cda631ee54800322b8
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-0a4i-9000000000-4f842c3673925d29c402
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-0udi-0900000000-5e751351656f6eb62de3
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , NegativeLC-MS/MSsplash10-001i-0910000000-7729faa24733fbad77b7
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, NegativeLC-MS/MSsplash10-0002-0900000000-c3c62f83bff99f44f7ab
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, NegativeLC-MS/MSsplash10-0zfr-6900000000-b6d8379db3e3f1480b14
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, NegativeLC-MS/MSsplash10-0a4i-9300000000-4fde39bb93cde5a27f23
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, NegativeLC-MS/MSsplash10-00i0-9000000000-4343832f3a55842423a9
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-2900000000-5aa3d6d620db1d733a65
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0m30-7900000000-fc77f69ad43f915bf23e
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6r-9000000000-c597f1f5e416037aa82d
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-2900000000-5aa3d6d620db1d733a65
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0m30-7900000000-fc77f69ad43f915bf23e
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6r-9000000000-c597f1f5e416037aa82d
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-1900000000-f2b463076a150a514f0c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0f9t-8900000000-b2d3fa8d7ab01a220d9a
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-053r-9100000000-554bfbd6839bc376cba0
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-1900000000-f2b463076a150a514f0c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0f9t-8900000000-b2d3fa8d7ab01a220d9a
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-053r-9100000000-554bfbd6839bc376cba0
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0002-0900000000-c3c62f83bff99f44f7ab
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0zfr-6900000000-b6d8379db3e3f1480b14
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4i-9300000000-4fde39bb93cde5a27f23
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-00i0-9000000000-4343832f3a55842423a9
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-9000000000-6e43f767847790112b65
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0udi-0900000000-1367eeeb6ad64c67a0aa
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-9000000000-4f842c3673925d29c402
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0udi-0900000000-5e751351656f6eb62de3
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as gamma-keto acids and derivatives. These are organic compounds containing an aldehyde substituted with a keto group on the C4 carbon atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Keto acids and derivatives
Sub Class
Gamma-keto acids and derivatives
Direct Parent
Gamma-keto acids and derivatives
Alternative Parents
Short-chain keto acids and derivatives / Dicarboxylic acids and derivatives / Alpha-keto acids and derivatives / Alpha-hydroxy ketones / Carboxylic acids / Organic oxides / Hydrocarbon derivatives
Substituents
Gamma-keto acid / Short-chain keto acid / Dicarboxylic acid or derivatives / Alpha-keto acid / Alpha-hydroxy ketone / Ketone / Carboxylic acid / Carboxylic acid derivative / Organic oxygen compound / Organic oxide
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
oxo dicarboxylic acid (CHEBI:30915)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
General Function
Pyridoxal phosphate binding
Specific Function
Not Available
Gene Name
aspC
Uniprot ID
P00509
Uniprot Name
Aspartate aminotransferase
Molecular Weight
43572.965 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Drug created on February 27, 2013 15:15 / Updated on January 05, 2018 13:27