Details of the Drug

General Information of Drug (ID: DMMB29S)

• Drug Name: Orotate
• Synonyms: 73-97-2; Orotic acidanion; AC1LSPNG; CHEBI:30839; CTK5D9013; DTXSID80363448; PXQPEWDEAKTCGB-UHFFFAOYSA-M; AG-G-93379; 2,4-dioxo-1H-pyrimidine-6-carboxylate; CJ-15820; 21317-EP2314295A1; 21317-EP2284172A1; 21317-EP2281559A1; 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylate; 4-Pyrimidinecarboxylicacid, 1,2,3,6-tetrahydro-2,6-dioxo-, ion(1-)

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 155.09
  Topological Polar Surface Area (xlogp); -0.8
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C5H3N2O4-
  IUPAC Name: 2,4-dioxo-1H-pyrimidine-6-carboxylate
  Canonical SMILES: C1=C(NC(=O)NC1=O)C(=O)[O-]
  InChI: InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11)/p-1
  InChIKey: PXQPEWDEAKTCGB-UHFFFAOYSA-M
• Cross-matching ID:
  PubChem CID: 1492348
  ChEBI ID: CHEBI:30839
  CAS Number: 73-97-2
  TTD ID: D0B1TS
  VARIDT ID: DR00157

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Plasmodium Dihydroorotase (Malaria dho)	TT09NOX	A9CSR1_PLAFA	Inhibitor	[1]
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase)	TT3PQ2Y	PYRD_PLAF7	Inhibitor	[1]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Urate anion exchanger 1 (SLC22A12)	DT2WLAD	S22AC_HUMAN	Substrate	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Urate anion exchanger 1 (SLC22A12)	DTP	URAT1	4.40E-01	-6.93E-03	-3.05E-02

References

• [1] Antimalarial activity of orotate analogs that inhibit dihydroorotase and dihydroorotate dehydrogenase. Biochem Pharmacol. 1992 Mar 17;43(6):1295-301.
• [2] Human urate transporter 1 (hURAT1) mediates the transport of orotate. J Physiol Sci. 2011 May;61(3):253-7.
• [3] Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone. Drug Metab Dispos. 2005 Dec;33(12):1791-5.
• [4] Concentration-dependent mode of interaction of angiotensin II receptor blockers with uric acid transporter. J Pharmacol Exp Ther. 2007 Jan;320(1):211-7.
• [5] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [6] Identification and characterization of potential new therapeutic targets in inflammatory and autoimmune diseases. Eur J Biochem. 1999 Dec;266(3):1184-91.
• [7] Expression and characterization of E. coli-produced soluble, functional human dihydroorotate dehydrogenase: a potential target for immunosuppression. J Mol Microbiol Biotechnol. 1999 Aug;1(1):183-8.
• [8] Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci. 2004 Apr;13(4):1031-42.
• [9] Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid. Chem Biol Interact. 2000 Jan 3;124(1):61-76.
• [10] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [11] Structure-activity relationships of pyrimidines as dihydroorotate dehydrogenase inhibitors. Biochem Pharmacol. 1988 Oct 15;37(20):3807-16.