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

General Information of Drug (ID: DMIQDFW)

• Drug Name: Neu-P11 Drug Info
• Synonyms: Piromelatine; UNII-S3UN2146K9; 946846-83-9; S3UN2146K9; NEU-P11; Piromelatine [INN]; NEU-P-11; SCHEMBL8235551; DTXSID90241566; N-(2-(5-Methoxy-1H-indol-3-yl)ethyl)-4-oxo-4H-pyran-2-carboxamide; 4H-Pyran-2-carboxamide, N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-oxo-; SB19819

Indication

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Phase 2	[1]
Dementia	6D80-6D86	Phase 2	[2]
Insomnia	7A00-7A0Z	Phase 2	[3]

• Cross-matching ID:
  PubChem CID: 24815904
  CAS Number: CAS 946846-83-9
  TTD Drug ID: DMIQDFW

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT 1D receptor (HTR1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[6]
Eletriptan	DMW649X	Migraine	8A80	Approved	[7]
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[7]
Frovatriptan	DM7RE8P	Migraine	8A80	Approved	[7]
Sumatriptan	DMVYXR8	Cluster headache	8A81.0	Approved	[8]
Rizatriptan	DMDJMA3	Migraine	8A80	Approved	[9]
Almogran	DM7I64Z	Migraine	8A80	Approved	[10]
FKB01MD	DM2O7NM	N. A.	N. A.	Phase 2	[11]
NXN-188	DMMBAIH	Migraine	8A80	Phase 2	[12]
TGBA01AD	DMJ2FTU	Mood disorder	6A60-6E23	Phase 2	[13]

Drug(s) Targeting 5-HT 1A receptor (HTR1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[7]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[14]
OPC-34712	DMHG57U	Major depressive disorder	6A70.3	Approved	[15]
Vilazodone	DM4LECQ	Major depressive disorder	6A70.3	Approved	[16]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[17]
Gepirone	DMGX5Q0	Major depressive disorder	6A70.3	Approved	[18]
TERTATOLOL	DM2L3D5	Hypertension	BA00-BA04	Approved	[19]
Urapidil	DMD59GI	Hypertension	BA00-BA04	Approved	[20]
Treximet	DMU54QB	Migraine	8A80	Approved	[21]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[22]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Melatonin	DMKWFBT	Depression	6A70-6A7Z	Approved	[23]
Ramelteon	DM7IW9J	Insomnia	7A00-7A0Z	Approved	[24]
Tasimelteon	DMLOQ1V	Insomnia	7A00-7A0Z	Approved	[25]
LY-156735	DM5IX9M	Anxiety disorder	6B00-6B0Z	Phase 2	[26]
Agomelatine	DMXYA5K	Major depressive disorder	6A70.3	Withdrawn from market	[27]
Luzindole	DMXRJQV	Sleep-wake disorder	7A00-7B2Z	Terminated	[28]
S-20928	DMQDWMJ	Sleep-wake disorder	7A00-7B2Z	Terminated	[29]
GR-133347	DMNRJA0	Anxiety disorder	6B00-6B0Z	Terminated	[30]
GR-131663	DMKAGLV	Anxiety disorder	6B00-6B0Z	Terminated	[31]
SL-18.1616	DMI1WNF	Insomnia	7A00-7A0Z	Terminated	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 1A receptor (HTR1A)	TTSQIFT	5HT1A_HUMAN	Agonist	[4]
5-HT 1D receptor (HTR1D)	TT6MSOK	5HT1D_HUMAN	Agonist	[4]
Melatonin receptor type 1A (MTNR1A)	TT0WAIE	MTR1A_HUMAN	Agonist	[5]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] ClinicalTrials.gov (NCT01489969) Sleep Laboratory Study to Investigate the Safety and Efficacy of Neu-P11 in Primary Insomnia Patients. U.S. National Institutes of Health.
• [4] Clinical pipeline report, company report or official report of Neurim Pharmaceuticals.
• [5] 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).
• [6] Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. Mol Pharmacol. 1991 Aug;40(2):143-8.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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• [9] An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc. 2002;45:199-210.
• [10] Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study. Clin Ther. 2001 Nov;23(11):1867-75.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Company report (NeurAxon)
• [13] Company report (Fabrekramer)
• [14] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [15] Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors.Pharmacol Biochem Behav.2014 Sep;124:245-9.
• [16] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [17] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [18] Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.
• [19] Synthesis of new derivatives of 8-OH-DPAT: Influence of substitution on the aromatic ring on the pharmacological profile, Bioorg. Med. Chem. Lett. 3(10):2035-2038 (1993).
• [20] Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.
• [21] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [22] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [23] 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.
• [24] MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014 Apr 24;57(8):3161-85.
• [25] 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).
• [26] Melatonin and sleep in aging population. Exp Gerontol. 2005 Dec;40(12):911-25.
• [27] Melatonin receptor agonists: SAR and applications to the treatment of sleep-wake disorders. Curr Top Med Chem. 2008;8(11):954-68.
• [28] Luzindole (N-0774): a novel melatonin receptor antagonist. J Pharmacol Exp Ther. 1988 Sep;246(3):902-10.
• [29] 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.
• [30] US patent application no. 5,151,446, Substituted 2-amidotetralins as melatonin agonists and antagonists.
• [31] 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.
• [32] US patent application no. 2005,016,4987, Melatonin combination therapy for improving sleep quality.