Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMXYA5K)

• Drug Name: Agomelatine Drug Info
• Synonyms: Thymanax; Valdoxan; Agomelatine [INN]; AGO 178; AGO178; S 20098; S20098; AGO-178; Agomelatine(INN); S-20098; Valdoxan (TN); Valdoxan, Melitor, Thymanax, Agomelatine; N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide; N-(2-(7-Methoxy-1-naphthalenyl)ethyl)acetamide; N-(2-(7-Methoxynaphth-1-yl)ethyl)acetamide; N-(2-(7-methoxy-1-naphthyl)ethyl)acetamide

Indication

Disease Entry	ICD 11	Status	REF
Major depressive disorder	6A70.3	Withdrawn from market	[1]

• Cross-matching ID:
  PubChem CID: 82148
  ChEBI ID: CHEMBL10878
  CAS Number: CAS 138112-76-2
  TTD Drug ID: DMXYA5K
  VARIDT Drug ID: DR00473
  INTEDE Drug ID: DR0053

Molecule-Related Drug Atlas

Drug(s) Targeting Melatonin receptor type 1A (MTNR1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Melatonin	DMKWFBT	Depression	6A70-6A7Z	Approved	[5]
Ramelteon	DM7IW9J	Insomnia	7A00-7A0Z	Approved	[6]
Tasimelteon	DMLOQ1V	Insomnia	7A00-7A0Z	Approved	[7]
Neu-P11	DMIQDFW	Alzheimer disease	8A20	Phase 2	[8]
LY-156735	DM5IX9M	Anxiety disorder	6B00-6B0Z	Phase 2	[9]
Luzindole	DMXRJQV	Sleep-wake disorder	7A00-7B2Z	Terminated	[10]
S-20928	DMQDWMJ	Sleep-wake disorder	7A00-7B2Z	Terminated	[11]
GR-133347	DMNRJA0	Anxiety disorder	6B00-6B0Z	Terminated	[12]
GR-131663	DMKAGLV	Anxiety disorder	6B00-6B0Z	Terminated	[13]
SL-18.1616	DMI1WNF	Insomnia	7A00-7A0Z	Terminated	[14]

Drug(s) Metabolized By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[15]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[21]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[22]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[23]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[24]

Drug(s) Affected By 5-hydroxytryptamine receptor 2C (HTR2C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[25]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[25]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[25]
Fluphenazine	DMIT8LX	Psychotic disorder	6A20-6A25	Approved	[26]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[27]
Nortriptyline	DM4KDYJ	Depression	6A70-6A7Z	Approved	[28]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[29]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[30]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[31]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Melatonin receptor type 1A (MTNR1A)	TT0WAIE	MTR1A_HUMAN	Agonist	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2) Main DME	DEJGDUW	CP1A2_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
5-hydroxytryptamine receptor 2C (HTR2C)	OT6H8DE0	5HT2C_HUMAN	Protein Interaction/Cellular Processes	[4]

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: 198).
• [2] Melatonin receptor agonists: SAR and applications to the treatment of sleep-wake disorders. Curr Top Med Chem. 2008;8(11):954-68.
• [3] Does celecoxib inhibit agomelatine metabolism via CYP2C9 or CYP1A2? Drug Des Devel Ther. 2018 Jul 11;12:2169-2172.
• [4] Design, synthesis and pharmacological evaluation of new series of naphthalenic analogues as melatoninergic (MT1/MT2) and serotoninergic 5-HT2C dual ligands (I). Eur J Med Chem. 2012 Mar;49:310-23.
• [5] The human MT1 melatonin receptor stimulates cAMP production in the human neuroblastoma cell line SH-SY5Y cells via a calcium-calmodulin signal transduction pathway. J Neuroendocrinol. 2005 Mar;17(3):170-8.
• [6] MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014 Apr 24;57(8):3161-85.
• [7] 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: 7393).
• [8] 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: 288).
• [9] Melatonin and sleep in aging population. Exp Gerontol. 2005 Dec;40(12):911-25.
• [10] Luzindole (N-0774): a novel melatonin receptor antagonist. J Pharmacol Exp Ther. 1988 Sep;246(3):902-10.
• [11] Effects of two melatonin analogues, S-20098 and S-20928, on melatonin receptors in the pars tuberalis of the rat. J Pineal Res. 1998 Oct;25(3):172-6.
• [12] US patent application no. 5,151,446, Substituted 2-amidotetralins as melatonin agonists and antagonists.
• [13] Novel non-indolic melatonin receptor agonists differentially entrain endogenous melatonin rhythm and increase its amplitude. Eur J Pharmacol. 1999 Oct 15;382(3):157-66.
• [14] US patent application no. 2005,016,4987, Melatonin combination therapy for improving sleep quality.
• [15] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [16] Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
• [17] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [18] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [19] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [20] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [21] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [22] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [23] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [24] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
• [25] Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulatio... Mol Pharmacol. 2008 Mar;73(3):748-57.
• [26] Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs. Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11927-32. doi: 10.1073/pnas.0609752104. Epub 2007 Jul 2.
• [27] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [28] Downregulation of serotonin receptor subtypes by nortriptyline and adinazolam in major depressive disorder: neuroendocrine and platelet markers. Clin Neuropharmacol. 1993;16 Suppl 3:S19-31.
• [29] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [30] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [31] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [32] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.