Details of the Drug

General Information of Drug (ID: DM5LFYN)

Drug Name
alpha-ketoglutaric acid
Synonyms 2-ketoglutarate; 2-oxoglutarate; alpha-ketoglutarate; 2-ketoglutaric acid; oxoglutarate
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Affected Organisms
Humans and other mammals
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 146.1
Logarithm of the Partition Coefficient (xlogp) -0.9
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C5H6O5
IUPAC Name
2-oxopentanedioic acid
Canonical SMILES
C(CC(=O)O)C(=O)C(=O)O
InChI
InChI=1S/C5H6O5/c6-3(5(9)10)1-2-4(7)8/h1-2H2,(H,7,8)(H,9,10)
InChIKey
KPGXRSRHYNQIFN-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
51
ChEBI ID
CHEMBL1686
CAS Number
328-50-7
UNII
8ID597Z82X
DrugBank ID
DB08845
TTD ID
D09KQZ
VARIDT ID
DR00139
INTEDE ID
DR2059
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Oxoglutarate receptor (OXGR1) TTAS1QK OXGR1_HUMAN Agonist [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Mitochondrial 2-oxodicarboxylate carrier (SLC25A21) DT2UQYR ODC_HUMAN Substrate [3]
Mitochondrial 2-oxoglutarate/malate carrier (SLC25A11) DT0YAUQ M2OM_HUMAN Substrate [4]
Sodium/dicarboxylate cotransporter 3 (SLC13A3) DTKXTPW S13A3_HUMAN Substrate [5]
Sodium-coupled citrate transporter (SLC13A5) DTFPWJ9 S13A5_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Prolyl 4-hydroxylase alpha-1 (P4HA1) DESO5ZY P4HA1_HUMAN Substrate [7]
Prolyl 4-hydroxylase alpha-2 (P4HA2) DE5EGK0 P4HA2_HUMAN Substrate [7]
HIF-prolyl hydroxylase 3 (EGLN3) DEMQTKH EGLN3_HUMAN Substrate [8]
HIF-prolyl hydroxylase 2 (EGLN1) DEWO724 EGLN1_HUMAN Substrate [8]
Factor inhibiting HIF-1 (HIF1AN) DEY1CBW HIF1N_HUMAN Substrate [9]
Prolyl 3-hydroxylase 1 (P3H1) DEW527E P3H1_HUMAN Substrate [10]
Prolyl 3-hydroxylase 2 (P3H2) DELB5PA P3H2_HUMAN Substrate [10]
Prolyl 4-hydroxylase alpha-3 (P4HA3) DE2L4RX P4HA3_HUMAN Substrate [11]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Gene/Protein Processing [12]
D-2-hydroxyglutarate dehydrogenase, mitochondrial (D2HGDH) OTLHXW69 D2HDH_HUMAN Biotransformations [13]
Integrin-binding sialoprotein (IBSP) OT29944Y SIAL_HUMAN Gene/Protein Processing [12]
Osteocalcin (BGLAP) OTK1YLWQ OSTCN_HUMAN Gene/Protein Processing [12]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Post-Translational Modifications [12]
Transcription factor Sp7 (SP7) OT07ETZT SP7_HUMAN Gene/Protein Processing [12]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3636).
2 Screening beta-arrestin recruitment for the identification of natural ligands for orphan G-protein-coupled receptors. J Biomol Screen. 2013 Jun;18(5):599-609.
3 Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease. Genet Med. 2018 Oct;20(10):1224-1235.
4 The mitochondrial dicarboxylate and 2-oxoglutarate carriers do not transport glutathione. FEBS Lett. 2015 Feb 27;589(5):621-8.
5 SLC13A3 variants cause acute reversible leukoencephalopathy and -ketoglutarate accumulation. Ann Neurol. 2019 Mar;85(3):385-395.
6 SLC13 family of Na+ coupled di- and tri-carboxylate/sulfate transporters. Mol Aspects Med. 2013 Apr-Jun;34(2-3):299-312.
7 Prolyl 4-hydroxylases, the key enzymes of collagen biosynthesis. Matrix Biol. 2003 Mar;22(1):15-24.
8 Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. J Biol Chem. 2003 Aug 15;278(33):30772-80.
9 The facial triad in the alpha-ketoglutarate dependent oxygenase FIH: a role for sterics in linking substrate binding to O2 activation. J Inorg Biochem. 2017 Jan;166:26-33.
10 Characterization of recombinant human prolyl 3-hydroxylase isoenzyme 2, an enzyme modifying the basement membrane collagen IV. J Biol Chem. 2008 Jul 11;283(28):19432-9.
11 Identification and characterization of a third human, rat, and mouse collagen prolyl 4-hydroxylase isoenzyme. J Biol Chem. 2003 Nov 28;278(48):47685-93.
12 Alpha ketoglutarate exerts a pro-osteogenic effect in osteoblast cell lines through activation of JNK and mTOR/S6K1/S6 signaling pathways. Toxicol Appl Pharmacol. 2019 Jul 1;374:53-64.
13 Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. Am J Hum Genet. 2005 Feb;76(2):358-60. doi: 10.1086/427890. Epub 2004 Dec 17.