Details of the Drug

General Information of Drug (ID: DMHV5NK)

• Drug Name: TOLOXATONE
• Synonyms: Toloxatone; 29218-27-7; Humoryl; Perenum; 5-(Hydroxymethyl)-3-(m-tolyl)oxazolidin-2-one; Toloxatone [INN]; Delalande 69276; Toloxatonum [INN-Latin]; Toloxatona [INN-Spanish]; 5-(Hydroxymethyl)-3-(3-methylphenyl)-2-oxazolidinone; EINECS 249-522-2; BRN 0527506; 69276 MD; CHEMBL18116; 2-oxazolidinone, 5-(hydroxymethyl)-3-(3-methylphenyl)-; 5-Hydroxymethyl-3-(m-tolyl)-2-oxazolidinone; 5-(Hydroxymethyl)-3-m-tolyl-2-oxazolidinone; Toloxatone (INN); 5-(hydroxymethyl)-3-m-tolyloxazolidin-2-one; 2-Oxazolidinone, 5-hydroxymethyl-3-(m-t

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); 207.23
  Topological Polar Surface Area (xlogp); 1.2
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  Bioavailability: 56% of drug becomes completely available to its intended biological destination(s) [2]
  Clearance: The drug is cleared by the liver [3]
  Elimination: 1% of drug is excreted unchanged in the urine [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1 - 3 hours [3]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.49% [4]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.5 L/kg [4]
• Chemical Identifiers:
  Formula: C11H13NO3
  IUPAC Name: 5-(hydroxymethyl)-3-(3-methylphenyl)-1,3-oxazolidin-2-one
  Canonical SMILES: CC1=CC(=CC=C1)N2CC(OC2=O)CO
  InChI: InChI=1S/C11H13NO3/c1-8-3-2-4-9(5-8)12-6-10(7-13)15-11(12)14/h2-5,10,13H,6-7H2,1H3
  InChIKey: MXUNKHLAEDCYJL-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 34521
  ChEBI ID: CHEBI:156575
  CAS Number: 29218-27-7
  DrugBank ID: DB09245
  TTD ID: D0V3NT

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Monoamine oxidase type A (MAO-A)	TT3WG5C	AOFA_HUMAN	Inhibitor	[1]
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Inhibitor	[5]

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
Monoamine oxidase type B (MAO-B)	DTT	MAOB	2.65E-02	1.12E-02	0.07
Monoamine oxidase type A (MAO-A)	DTT	MAOA	8.14E-01	0.05	0.1

References

• [1] Quercetin as the active principle of Hypericum hircinum exerts a selective inhibitory activity against MAO-A: extraction, biological analysis, and ... J Nat Prod. 2006 Jun;69(6):945-9.
• [2] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [3] [Pharmacokinetics and metabolism of reversible MAO-A inhibitors in the human]. Psychiatr Prax. 1989 Aug;16 Suppl 1:11-7.
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] 3-(1H-Pyrrol-1-yl)-2-oxazolidinones as reversible, highly potent, and selective inhibitors of monoamine oxidase type A. J Med Chem. 2002 Mar 14;45(6):1180-3.
• [6] Emerging drugs for Parkinson's disease. Expert Opin Emerg Drugs. 2006 Sep;11(3):403-17.
• [7] Limitation of adipose tissue enlargement in rats chronically treated with semicarbazide-sensitive amine oxidase and monoamine oxidase inhibitors. Pharmacol Res. 2008 Jun;57(6):426-34.
• [8] Tranylcypromine: new perspectives on an "old" drug. Eur Arch Psychiatry Clin Neurosci. 2006 Aug;256(5):268-73.
• [9] 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. (Target id: 2490).
• [10] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [11] Glyceraldehyde-3-phosphate dehydrogenase-monoamine oxidase B-mediated cell death-induced by ethanol is prevented by rasagiline and 1-R-aminoindan. Neurotox Res. 2009 Aug;16(2):148-59.
• [12] Novel monoamine oxidase inhibitors, 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives, and their differential reversibility. Jpn J Pharmacol. 2002 Feb;88(2):174-82.
• [13] Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells. Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H821-8.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [15] Multiple mechanisms of action: the pharmacological profile of budipine. J Neural Transm Suppl. 1999;56:83-105.
• [16] Efficacy of citalopram and moclobemide in patients with social phobia: some preliminary findings. Hum Psychopharmacol. 2002 Dec;17(8):401-5.
• [17] Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice. Int J Neuropsychopharmacol. 2009 Mar 11:1-11.
• [18] Further investigation into the mechanism of tachykinin NK(2) receptor-triggered serotonin release from guinea-pig proximal colon. J Pharmacol Sci. 2009 May;110(1):122-6.
• [19] MAOIs in the contemporary treatment of depression. Neuropsychopharmacology. 1995 May;12(3):185-219.
• [20] Binding of beta-carbolines at imidazoline I2 receptors: a structure-affinity investigation. Bioorg Med Chem Lett. 2004 Feb 23;14(4):999-1002.
• [21] Inhibition of rat brain monoamine oxidase activities by psoralen and isopsoralen: implications for the treatment of affective disorders. Pharmacol Toxicol. 2001 Feb;88(2):75-80.
• [22] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [23] Ladostigil: a novel multimodal neuroprotective drug with cholinesterase and brain-selective monoamine oxidase inhibitory activities for Alzheimer's disease treatment. Curr Drug Targets. 2012 Apr;13(4):483-94.
• [24] Reversible inhibitors of monoamine oxidase-A (RIMAs): robust, reversible inhibition of human brain MAO-A by CX157. Neuropsychopharmacology. 2010 Feb;35(3):623-31.
• [25] Proposed structural basis of interaction of piperine and related compounds with monoamine oxidases. Bioorg Med Chem Lett. 2010 Jan 15;20(2):537-40.