Details of the Drug

General Information of Drug (ID: DMUK75B)

• Drug Name: Urea
• Synonyms: carbamide; 57-13-6; Isourea; Carbonyldiamide; Ureophil; Carbonyldiamine; Carbamimidic acid; Pseudourea; Ureaphil; Urevert; Carbaderm; Alphadrate; Keratinamin; Calmurid; Aquadrate; Carbonyl diamide; Pastaron; Urepearl; Carbamide resin; Ultra Mide; Varioform ii; Aqua Care; Prespersion, 75 urea; carmol; basodexan; Harnstoff; Nutraplus; Mocovina; Urea solution; Supercel 3000; Aqua Care HP; Ureacin-20; Ureacin-40 Creme; Ureacin-10 lotion; Polyurea; Panafil; Onychomal; Hyanit; Caswell No. 902; Carbonyl Diamine; Mocovina [Czech]; Harnstoff [Ge

Indication

Disease Entry	ICD 11	Status	REF
Dermatological disease	DA24.Y	Approved	[1]
Exanthem	N.A.	Approved	[2]
Impacted cerumen	AA42	Approved	[2]
Pityriasis simplex	N.A.	Approved	[2]
Skin disease	EA00-EM0Z	Approved	[2]
Tinea versicolor	1F2D.0	Approved	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 60.056
  Logarithm of the Partition Coefficient (xlogp); -1.4
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 1

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Renal failure chronic	Not Available	PTH1R	OTQF5ZAK	[3]
Renal failure chronic	Not Available	HBA1	OTW2BQF4	[3]

• Chemical Identifiers:
  Formula: CH4N2O
  IUPAC Name: urea
  Canonical SMILES: C(=O)(N)N
  InChI: InChI=1S/CH4N2O/c2-1(3)4/h(H4,2,3,4)
  InChIKey: XSQUKJJJFZCRTK-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 1176
  ChEBI ID: CHEBI:16199
  CAS Number: 57-13-6
  DrugBank ID: DB03904
  TTD ID: D02XBW
  VARIDT ID: DR00048
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[5]
Alpha-fetoprotein (AFP)	OT9GG3ZI	FETA_HUMAN	Gene/Protein Processing	[6]
Aquaporin-10 (AQP10)	OT8Q5UWS	AQP10_HUMAN	Regulation of Drug Effects	[7]
Aquaporin-9 (AQP9)	OTLGH5ZY	AQP9_HUMAN	Regulation of Drug Effects	[8]
Arginase-2, mitochondrial (ARG2)	OTCPI0E8	ARGI2_HUMAN	Biotransformations	[9]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A)	OTI862QH	CPT1A_HUMAN	Gene/Protein Processing	[10]
Fibroblast growth factor receptor 1 (FGFR1)	OT4GLCXW	FGFR1_HUMAN	Gene/Protein Processing	[11]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Gene/Protein Processing	[12]
Hemoglobin subunit alpha (HBA1)	OTW2BQF4	HBA_HUMAN	Drug Response	[3]
Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R)	OTQF5ZAK	PTH1R_HUMAN	Drug Response	[3]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Urea (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Levomilnacipran	DMV26S8	Moderate	Increased risk of hyponatremia by the combination of Urea and Levomilnacipran.	Chronic pain [MG30]	[13]
Vilazodone	DM4LECQ	Moderate	Increased risk of hyponatremia by the combination of Urea and Vilazodone.	Depression [6A70-6A7Z]	[13]
Vortioxetine	DM6F1PU	Moderate	Increased risk of hyponatremia by the combination of Urea and Vortioxetine.	Depression [6A70-6A7Z]	[13]
Milnacipran	DMBFE74	Moderate	Increased risk of hyponatremia by the combination of Urea and Milnacipran.	Depression [6A70-6A7Z]	[13]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of hyponatremia by the combination of Urea and Desvenlafaxine.	Depression [6A70-6A7Z]	[13]
Eslicarbazepine	DMZREFQ	Moderate	Increased risk of hyponatremia by the combination of Urea and Eslicarbazepine.	Epilepsy/seizure [8A61-8A6Z]	[14]

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: 4539).
• [2] Urea FDA Label
• [3] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [4] Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.
• [5] Urea-induced denaturation of human serum albumin labeled with acrylodan. J Protein Chem. 2002 Feb;21(2):75-9. doi: 10.1023/a:1014508610017.
• [6] Carcinoembryonic antigen, alpha-fetoprotein, and prostate-specific antigen in the sera of industrial workers exposed to phenol, formaldehyde, urea, and mixed vapors. Inhal Toxicol. 2006 Dec;18(13):1041-6. doi: 10.1080/08958370600904603.
• [7] Cloning and identification of a new member of water channel (AQP10) as an aquaglyceroporin. Biochim Biophys Acta. 2002 Jul 19;1576(3):335-40. doi: 10.1016/s0167-4781(02)00393-7.
• [8] Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes permeable to water and urea, but not to glycerol. Biochem Biophys Res Commun. 1998 Mar 6;244(1):268-74. doi: 10.1006/bbrc.1998.8252.
• [9] Cells for bioartificial liver devices: the human hepatoma-derived cell line C3A produces urea but does not detoxify ammonia. Biotechnol Bioeng. 2008 Feb 15;99(3):644-51. doi: 10.1002/bit.21599.
• [10] Activation of peroxisome proliferator-activated receptor alpha by substituted urea-derived soluble epoxide hydrolase inhibitors. J Pharmacol Exp Ther. 2005 Jul;314(1):260-70. doi: 10.1124/jpet.105.085605. Epub 2005 Mar 29.
• [11] Synthesis and structure-activity relationships of soluble 7-substituted 3-(3,5-dimethoxyphenyl)-1,6-naphthyridin-2-amines and related ureas as dual inhibitors of the fibroblast growth factor receptor-1 and vascular endothelial growth factor receptor-2 tyrosine kinases. J Med Chem. 2005 Jul 14;48(14):4628-53. doi: 10.1021/jm0500931.
• [12] Urea and hypertonicity increase expression of heme oxygenase-1 in murine renal medullary cells. Am J Physiol Renal Physiol. 2001 Nov;281(5):F983-91. doi: 10.1152/ajprenal.0358.2000.
• [13] Product Information. Savella (milnacipran). Forest Pharmaceuticals, St. Louis, MO.
• [14] Product Information. Aptiom (eslicarbazepine). Sunovion Pharmaceuticals Inc, Marlborough, MA.