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]
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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: CHEBI:30915
CAS Number: 328-50-7
TTD ID: D09KQZ
VARIDT ID: DR00139
INTEDE ID: DR2059

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]

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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]

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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]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL)	OTG7J4BP	PPBT_HUMAN	Gene/Protein Processing	[12]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Gene/Protein Processing	[12]
D-2-hydroxyglutarate dehydrogenase, mitochondrial (D2HGDH)	OTLHXW69	D2HDH_HUMAN	Biotransformations	[13]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Gene/Protein Processing	[14]
Integrin-binding sialoprotein (IBSP)	OT29944Y	SIAL_HUMAN	Gene/Protein Processing	[12]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Gene/Protein Processing	[12]
Osteopontin (SPP1)	OTJGC23Y	OSTP_HUMAN	Gene/Protein Processing	[12]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Post-Translational Modifications	[12]
Runt-related transcription factor 2 (RUNX2)	OT97RQQM	RUNX2_HUMAN	Gene/Protein Processing	[12]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Post-Translational Modifications	[12]

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Molecular Interaction Atlas (MIA)

MIA Detail

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.
14	Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.