Details of the Drug

General Information of Drug (ID: DM5S4GK)

• Drug Name: Flavin-Adenine Dinucleotide
• Synonyms: flavin adenine dinucleotide; Flavin-adenine dinucleotide; 146-14-5; FAD; flavitan; Flavine-adenine dinucleotide; Flanin F; UNII-ZC44YTI8KK; Flamitajin B; Adenine-flavin dinucleotide; Adenine-flavine dinucleotide; ZC44YTI8KK; Flavine adenosine diphosphate; Riboflavin 5'-adenosine diphosphate; Flaziren (free acid); Riboflavin-adenine dinucleotide; Adenine-riboflavin dinucleotide; Adenine-riboflavine dinucleotide; Riboflavine-adenine dinucleotide; Isoalloxazine-adenine dinucleotide; Flavin adenin dinucleotide; CHEBI:16238; flavin a

Indication

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

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 5:
  Molecular Weight (mw); 785.5
  Topological Polar Surface Area (xlogp); -5
  Rotatable Bond Count (rotbonds); 13
  Hydrogen Bond Donor Count (hbonddonor); 9
  Hydrogen Bond Acceptor Count (hbondacc); 20
• Chemical Identifiers:
  Formula: C27H33N9O15P2
  IUPAC Name: [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4S)-5-(7,8-dimethyl-2,4-dioxobenzo[g]pteridin-10-yl)-2,3,4-trihydroxypentyl] hydrogen phosphate
  Canonical SMILES: CC1=CC2=C(C=C1C)N(C3=NC(=O)NC(=O)C3=N2)C[C@@H]([C@@H]([C@@H](COP(=O)(O)OP(=O)(O)OC[C@@H]4[C@H]([C@H]([C@@H](O4)N5C=NC6=C(N=CN=C65)N)O)O)O)O)O
  InChI: InChI=1S/C27H33N9O15P2/c1-10-3-12-13(4-11(10)2)35(24-18(32-12)25(42)34-27(43)33-24)5-14(37)19(39)15(38)6-48-52(44,45)51-53(46,47)49-7-16-20(40)21(41)26(50-16)36-9-31-17-22(28)29-8-30-23(17)36/h3-4,8-9,14-16,19-21,26,37-41H,5-7H2,1-2H3,(H,44,45)(H,46,47)(H2,28,29,30)(H,34,42,43)/t14-,15+,16+,19-,20+,21+,26+/m0/s1
  InChIKey: VWWQXMAJTJZDQX-UYBVJOGSSA-N
• Cross-matching ID:
  PubChem CID: 643975
  ChEBI ID: CHEBI:16238
  CAS Number: 146-14-5
  DrugBank ID: DB03147
  TTD ID: D00IMW

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Flavohemoglobin (Bact hmp)	TTNAW8S	HMP_ECOLI	Inhibitor	[2]
Bacterial Fumarate reductase flavoprotein (Bact frdA)	TTHDSE2	FRDA_HELPY	Inhibitor	[2]
Bacterial UDP-N-acetylenolpyruvylglucosamine reductase (Bact murB)	TTAEOJ4	MURB_ECOLI	Inhibitor	[2]
Cytoplasmic thioredoxin reductase (TXNRD1)	TTR7UJ3	TRXR1_HUMAN	Inhibitor	[2]
Dihydrothymine dehydrogenase (DPYD)	TTZPS91	DPYD_HUMAN	Inhibitor	[2]
Glutathione reductase (GR)	TTEP6RV	GSHR_HUMAN	Inhibitor	[2]
Monoamine oxidase type A (MAO-A)	TT3WG5C	AOFA_HUMAN	Inhibitor	[2]
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Inhibitor	[2]
Nitric-oxide synthase brain (NOS1)	TTZUFI5	NOS1_HUMAN	Inhibitor	[2]
Quinone reductase 1 (NQO1)	TT8XK6L	NQO1_HUMAN	Inhibitor	[2]
Quinone reductase 2 (NQO2)	TTJLP0R	NQO2_HUMAN	Inhibitor	[2]
Trypanosoma Dihydrolipoamide dehydrogenase (Trypano LPD)	TTBKQL3	DLDH_TRYCR	Inhibitor	[2]
Trypanosoma Trypanothione reductase (Trypano TPR)	TTRTKPV	TYTR_TRYBB	Inhibitor	[2]
Xanthine dehydrogenase/oxidase (XDH)	TT7RJY8	XDH_HUMAN	Inhibitor	[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
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] 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: 5184).
• [2] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] ClinicalTrials.gov (NCT01748877) Efficacy, Tolerability, and Safety of NXN-462 in Patients With Post-Herpetic Neuralgia. U.S. National Institutes of Health.
• [5] Discovery of a series of aminopiperidines as novel iNOS inhibitors. Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43.
• [6] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [7] Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fl... J Med Chem. 2009 Apr 23;52(8):2443-53.
• [8] Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases. Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.
• [9] The purification and properties of glutathione reductase from the cestode Moniezia expansa. Int J Biochem Cell Biol. 1995 Apr;27(4):393-401.
• [10] Thioredoxin reductase inhibitors: a patent review.Expert Opin Ther Pat. 2017 May;27(5):547-556.
• [11] Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate. J Med Chem. 2005 Nov 17;48(23):7400-10.
• [12] In vitro inhibition of human erythrocyte glutathione reductase by some new organic nitrates. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3661-3.
• [13] Fumarate reductase is essential for Helicobacter pylori colonization of the mouse stomach. Microb Pathog. 2000 Nov;29(5):279-87.
• [14] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [15] Allopurinol: xanthine oxidase inhibitor. Tex Med. 1966 Jan;62(1):100-1.
• [16] Clinical pipeline report, company report or official report of Takeda (2009).
• [17] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [18] Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J Nat Prod. 2009 Apr;72(4):725-31.
• [19] Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol. 1988 Jan 15;37(2):349-52.
• [20] Inhibition of cow's milk xanthine oxidase by flavonoids. J Nat Prod. 1988 Mar-Apr;51(2):345-8.
• [21] QT/QTc study conducted in Japanese adult healthy subjects: a novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation. J Clin Pharmacol. 2014 Apr;54(4):446-52.
• [22] Clinical pipeline report, company report or official report of Teijin Pharma.
• [23] Pharmacokinetics, pharmacodynamics, and tolerability of LC350189, a novel xanthine oxidase inhibitor, in healthy subjects. Drug Des Devel Ther. 2015 Aug 31;9:5033-49.
• [24] An updated patent review: xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015).Expert Opin Ther Pat. 2017 Mar;27(3):311-345.
• [25] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [26] Therapeutic strategies for Leber's hereditary optic neuropathy: A current update. Intractable Rare Dis Res. 2013 November; 2(4): 130-135.
• [27] In silico identification and biochemical characterization of novel inhibitors of NQO1. Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54.
• [28] In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
• [29] Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: quinone oxidoreductase-1 (NQO1). J Med Chem. 2009 Nov 26;52(22):7142-56.
• [30] Imidazoacridin-6-ones as novel inhibitors of the quinone oxidoreductase NQO2. Bioorg Med Chem Lett. 2010 May 1;20(9):2832-6.
• [31] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [32] Synthesis of casimiroin and optimization of its quinone reductase 2 and aromatase inhibitory activities. J Med Chem. 2009 Apr 9;52(7):1873-84.
• [33] Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer. Bioorg Med Chem. 2010 Jul 15;18(14):5352-66.
• [34] Enhancement of the antitumour activity of 5-fluorouracil (5-FU) by inhibiting dihydropyrimidine dehydrogenase activity (DPD) using 5-chloro-2,4-dihydroxypyridine (CDHP) in human tumour cells. Eur J Cancer. 2002 Jun;38(9):1271-7.
• [35] Eniluracil: an irreversible inhibitor of dihydropyrimidine dehydrogenase. Expert Opin Investig Drugs. 2000 Jul;9(7):1635-49.
• [36] Single ascending dose tolerability, pharmacokinetic-pharmacodynamic study of dihydropyrimidine dehydrogenase inhibitor Ro 09-4889. Clin Cancer Res. 2004 Apr 1;10(7):2327-35.
• [37] Effects of FL-386 on faecal lipid excretion in humans. J Int Med Res. 1993 Sep-Oct;21(5):225-33.
• [38] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [39] Emerging drugs for Parkinson's disease. Expert Opin Emerg Drugs. 2006 Sep;11(3):403-17.
• [40] 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.
• [41] Tranylcypromine: new perspectives on an "old" drug. Eur Arch Psychiatry Clin Neurosci. 2006 Aug;256(5):268-73.
• [42] 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).
• [43] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [44] 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.
• [45] Novel monoamine oxidase inhibitors, 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives, and their differential reversibility. Jpn J Pharmacol. 2002 Feb;88(2):174-82.
• [46] Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells. Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H821-8.
• [47] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [48] Multiple mechanisms of action: the pharmacological profile of budipine. J Neural Transm Suppl. 1999;56:83-105.
• [49] Efficacy of citalopram and moclobemide in patients with social phobia: some preliminary findings. Hum Psychopharmacol. 2002 Dec;17(8):401-5.
• [50] 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.
• [51] 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.
• [52] MAOIs in the contemporary treatment of depression. Neuropsychopharmacology. 1995 May;12(3):185-219.
• [53] Binding of beta-carbolines at imidazoline I2 receptors: a structure-affinity investigation. Bioorg Med Chem Lett. 2004 Feb 23;14(4):999-1002.
• [54] 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.
• [55] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [56] 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.
• [57] Reversible inhibitors of monoamine oxidase-A (RIMAs): robust, reversible inhibition of human brain MAO-A by CX157. Neuropsychopharmacology. 2010 Feb;35(3):623-31.
• [58] Proposed structural basis of interaction of piperine and related compounds with monoamine oxidases. Bioorg Med Chem Lett. 2010 Jan 15;20(2):537-40.
• [59] Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
• [60] 8-Methoxy-naphtho[2,3-b]thiophen-4,9-quinone, a non-competitive inhibitor of trypanothione reductase. Mem Inst Oswaldo Cruz. 2003 Jun;98(4):565-8.
• [61] The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors. Bioorg Med Chem. 2008 Jul 15;16(14):6689-95.
• [62] Antitrypanosomal, antileishmanial, and antimalarial activities of quaternary arylalkylammonium 2-amino-4-chlorophenyl phenyl sulfides, a new class ... J Med Chem. 2005 Dec 15;48(25):8087-97.