Details of the Drug

General Information of Drug (ID: DM4UXT1)

• Drug Name: Tyramine
• Synonyms: Tyramine; 4-(2-Aminoethyl)phenol; 51-67-2; 4-Hydroxyphenethylamine; p-Tyramine; 2-(4-Hydroxyphenyl)ethylamine; Uteramine; Tyramin; Tyrosamine; Tocosine; 4-Hydroxyphenylethylamine; Systogene; Phenol, 4-(2-aminoethyl)-; p-Hydroxyphenethylamine; Tenosin-wirkstoff; p-Hydroxyphenylethylamine; p-(2-Aminoethyl)phenol; 2-(p-Hydroxyphenyl)ethylamine; Phenethylamine, p-hydroxy-; p-beta-Aminoethylphenol; Phenol, p-(2-aminoethyl)-; Benzeneethanamine, 4-hydroxy-; Tyramine base; beta-Hydroxyphenylethylamine; NSC 249188; p-tyramine; [3H]tyramine

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 137.18
  Topological Polar Surface Area (xlogp); 1.1
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 2
• Chemical Identifiers:
  Formula: C8H11NO
  IUPAC Name: 4-(2-aminoethyl)phenol
  Canonical SMILES: C1=CC(=CC=C1CCN)O
  InChI: InChI=1S/C8H11NO/c9-6-5-7-1-3-8(10)4-2-7/h1-4,10H,5-6,9H2
  InChIKey: DZGWFCGJZKJUFP-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5610
  ChEBI ID: CHEBI:15760
  CAS Number: 51-67-2
  DrugBank ID: DB08841
  TTD ID: D0C5RZ
  VARIDT ID: DR01389
  INTEDE ID: DR2043

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Trace amine-associated receptor-1 (TAAR1)	TTIU98M	TAAR1_HUMAN	Agonist	[3], [4]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Copper amine oxidase (AOC3)	DE6SOC5	AOC3_HUMAN	Substrate	[6]
Semicarbazide-sensitive amine oxidase (AOC2)	DE8DP90	AOC2_HUMAN	Substrate	[6]

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
Trace amine-associated receptor-1 (TAAR1)	DTT	TAAR1	6.12E-01	-0.01	-0.06
Organic cation transporter 1 (SLC22A1)	DTP	SLC22A1	5.15E-01	1.61E-02	7.93E-02
Semicarbazide-sensitive amine oxidase (AOC2)	DME	AOC2	2.67E-01	8.39E-02	3.04E-01
Copper amine oxidase (AOC3)	DME	AOC3	7.70E-01	-1.74E-02	-5.23E-02

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: 2148).
• [2] 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: 2150).
• [3] Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists. PLoS One. 2011;6(10):e27073.
• [4] Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):8966-71.
• [5] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [6] The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase. Cell Mol Life Sci. 2009 Aug;66(16):2743-57.
• [7] Metabolism of tresperimus by rat aorta semicarbazide-sensitive amine oxidase (SSAO). Fundam Clin Pharmacol. 2002 Dec;16(6):461-70.
• [8] Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
• [9] Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family). J Pharmacol Exp Ther. 2006 Nov;319(2):879-86.
• [10] Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leuk Lymphoma. 2008 Apr;49(4):639-42.
• [11] Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57.
• [12] Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
• [13] Upregulation of histone acetylation reverses organic anion transporter 2 repression and enhances 5-fluorouracil sensitivity in hepatocellular carcinoma
• [14] Comparison of type I and type II organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5.
• [15] Organic cation transporters and their pharmacokinetic and pharmacodynamic consequences. Drug Metab Pharmacokinet. 2008;23(4):243-53.
• [16] Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
• [17] Methamphetamine and HIV-1-induced neurotoxicity: role of trace amine associated receptor 1 cAMP signaling in astrocytes. Neuropharmacology. 2014 Oct;85:499-507.
• [18] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [19] Diagnostic pharmacology of the pupil.Clin Neuropharmacol.1985;8(1):27-37.
• [20] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [21] Clinical pipeline report, company report or official report of Roche.
• [22] The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20081-6.
• [23] The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia. Genes Brain Behav. 2007 Oct;6(7):628-39.