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

General Information of Drug (ID: DMEMN0W)

• Drug Name: 4P-PDOT Drug Info
• Synonyms: N-(4-phenyltetralin-2-yl)propanamide; 4-phenyl-2-propionamidotetraline

Indication

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

• Cross-matching ID:
  PubChem CID: 3976006
  ChEBI ID: CHEBI:110160
  CAS Number: CAS 134865-74-0
  TTD Drug ID: DMEMN0W

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	[4]
Ramelteon	DM7IW9J	Insomnia	7A00-7A0Z	Approved	[5]
Tasimelteon	DMLOQ1V	Insomnia	7A00-7A0Z	Approved	[6]
Neu-P11	DMIQDFW	Alzheimer disease	8A20	Phase 2	[7]
LY-156735	DM5IX9M	Anxiety disorder	6B00-6B0Z	Phase 2	[8]
Agomelatine	DMXYA5K	Major depressive disorder	6A70.3	Withdrawn from market	[9]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]
Resveratrol	DM3RWXL	Giant cell arteritis	4A44.2	Phase 3	[14]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[15]
Agomelatine	DMXYA5K	Major depressive disorder	6A70.3	Withdrawn from market	[16]
CHRYSOERIOL	DM96ECL	Discovery agent	N.A.	Investigative	[14]

Drug(s) Affected By Melatonin receptor type 1B (MTNR1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[17]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[18]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[19]
Melatonin	DMKWFBT	Depression	6A70-6A7Z	Approved	[20]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[21]
Resveratrol	DM3RWXL	Giant cell arteritis	4A44.2	Phase 3	[14]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[15]
Agomelatine	DMXYA5K	Major depressive disorder	6A70.3	Withdrawn from market	[16]
CHRYSOERIOL	DM96ECL	Discovery agent	N.A.	Investigative	[14]

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	Antagonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Melatonin receptor type 1A (MTNR1A)	OTYYV8JK	MTR1A_HUMAN	Protein Interaction/Cellular Processes	[3]
Melatonin receptor type 1B (MTNR1B)	OT6VFHX9	MTR1B_HUMAN	Protein Interaction/Cellular Processes	[3]

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: 1358).
• [2] Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms. FASEB J. 1998 Sep;12(12):1211-20.
• [3] Toward the definition of stereochemical requirements for MT2-selective antagonists and partial agonists by studying 4-phenyl-2-propionamidotetralin derivatives. J Med Chem. 2011 Dec 22;54(24):8362-72. doi: 10.1021/jm200790v. Epub 2011 Nov 18.
• [4] 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.
• [5] MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014 Apr 24;57(8):3161-85.
• [6] 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).
• [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. (Target id: 288).
• [8] Melatonin and sleep in aging population. Exp Gerontol. 2005 Dec;40(12):911-25.
• [9] Melatonin receptor agonists: SAR and applications to the treatment of sleep-wake disorders. Curr Top Med Chem. 2008;8(11):954-68.
• [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] Old and new inhibitors of quinone reductase 2. Chem Biol Interact. 2010 Jul 30;186(2):103-9. doi: 10.1016/j.cbi.2010.04.006. Epub 2010 May 4.
• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [16] Synthesis of phenalene and acenaphthene derivatives as new conformationally restricted ligands for melatonin receptors. J Med Chem. 2000 Nov 2;43(22):4051-62. doi: 10.1021/jm000922c.
• [17] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [18] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [19] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [20] Melatonin antagonizes apoptosis via receptor interaction in U937 monocytic cells. J Pineal Res. 2007 Sep;43(2):154-62. doi: 10.1111/j.1600-079X.2007.00455.x.
• [21] Common genetic variation in MTNR1B is associated with serum testosterone, glucose tolerance, and insulin secretion in polycystic ovary syndrome patients. Fertil Steril. 2010 Nov;94(6):2486-9, 2489.e1-2. doi: 10.1016/j.fertnstert.2010.01.059. Epub 2010 Mar 6.