Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT32JK8)

• DTT Name: Melatonin receptor type 1B (MTNR1B)
• Synonyms: Mel1b receptor; Mel1b melatonin receptor; Mel-1B-R
• Gene Name: MTNR1B
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: MTR1B_HUMAN
• TTD ID: T48268
• Sequence:
  MSENGSFANCCEAGGWAVRPGWSGAGSARPSRTPRPPWVAPALSAVLIVTTAVDVVGNLL
  VILSVLRNRKLRNAGNLFLVSLALADLVVAFYPYPLILVAIFYDGWALGEEHCKASAFVM
  GLSVIGSVFNITAIAINRYCYICHSMAYHRIYRRWHTPLHICLIWLLTVVALLPNFFVGS
  LEYDPRIYSCTFIQTASTQYTAAVVVIHFLLPIAVVSFCYLRIWVLVLQARRKAKPESRL
  CLKPSDLRSFLTMFVVFVIFAICWAPLNCIGLAVAINPQEMAPQIPEGLFVTSYLLAYFN
  SCLNAIVYGLLNQNFRREYKRILLALWNPRHCIQDASKGSHAEGLQSPAPPIIGVQHQAD
  AL
• Function: Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity. High affinity receptor for melatonin.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Circadian entrainment (hsa04713)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Class A/1 (Rhodopsin-like receptors) (R-HSA-373076)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ramelteon	DM7IW9J	Insomnia	7A00-7A0Z	Approved	[2]
Tasimelteon	DMLOQ1V	Insomnia	7A00-7A0Z	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VLB-01	DMQGV5P	Epilepsy	8A60-8A68	Phase 3	[3]

19 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-iodo-melatonin	DMSEIUP	Discovery agent	N.A.	Investigative	[4]
5-methoxycarbonylamino-N-acetyltryptamine	DMCZSP3	Discovery agent	N.A.	Investigative	[5]
Beta,beta-dimethylmelatonin	DM6FHQD	Discovery agent	N.A.	Investigative	[6]
Beta-methylmelatonin	DMKH32S	Discovery agent	N.A.	Investigative	[6]
N-(2,3,4,9-Tetrahydro-1H-carbazol-3-yl)-acetamide	DMWC70I	Discovery agent	N.A.	Investigative	[7]
N-(2-(5-methoxybenzofuran-3-yl)ethyl)acetamide	DM4V7AS	Discovery agent	N.A.	Investigative	[5]
N-(3-(2,5-dimethoxyphenyl)propyl)acetamide	DM4ZTF1	Discovery agent	N.A.	Investigative	[8]
N-(3-(2-ethoxy-5-methoxyphenyl)propyl)acetamide	DMLWGPC	Discovery agent	N.A.	Investigative	[8]
N-(3-(2-hydroxy-5-methoxyphenyl)propyl)acetamide	DMI452E	Discovery agent	N.A.	Investigative	[8]
N-(3-(3-methoxyphenyl)-3-phenylallyl)acetamide	DMH0LOT	Discovery agent	N.A.	Investigative	[9]
N-(3-(3-methoxyphenyl)propyl)acetamide	DMSZ03N	Discovery agent	N.A.	Investigative	[8]
N-(3-(3-methoxyphenyl)propyl)propionamide	DMKSM5A	Discovery agent	N.A.	Investigative	[8]
N-(3-(4-hydroxy-3-methoxyphenyl)propyl)acetamide	DMILWPS	Discovery agent	N.A.	Investigative	[8]
N-(3-(5-methoxy-2-propoxyphenyl)propyl)acetamide	DMHM0WI	Discovery agent	N.A.	Investigative	[8]
N-(3-Benzooxazol-7-yl-propyl)-acetamide	DMYSURL	Discovery agent	N.A.	Investigative	[10]
N-(3-Benzooxazol-7-yl-propyl)-butyramide	DMKMESD	Discovery agent	N.A.	Investigative	[10]
N-(3-Benzooxazol-7-yl-propyl)-propionamide	DMEMYS1	Discovery agent	N.A.	Investigative	[10]
N-[3-(2-Ethyl-benzooxazol-7-yl)-propyl]-acetamide	DMU89FH	Discovery agent	N.A.	Investigative	[10]
UCM-454	DMSVJFG	Discovery agent	N.A.	Investigative	[9]

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: 7393).
• [2] MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014 Apr 24;57(8):3161-85.
• [3] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [4] Synthesis of nitroindole derivatives with high affinity and selectivity for melatoninergic binding sites MT(3). J Med Chem. 2002 Apr 25;45(9):1853-9.
• [5] Design and synthesis of benzofuranic derivatives as new ligands at the melatonin-binding site MT3. Bioorg Med Chem. 2008 May 1;16(9):4954-62.
• [6] Mapping the melatonin receptor. 7. Subtype selective ligands based on beta-substituted N-acyl-5-methoxytryptamines and beta-substituted N-acyl-5-me... J Med Chem. 2006 Jun 15;49(12):3509-19.
• [7] Mapping the melatonin receptor. 2. synthesis and biological activity of indole derived melatonin analogues with restricted conformations of the C-3 amidoethane side chain, Bioorg. Med. Chem. Lett. 4(13):1559-1564 (1994).
• [8] Synthesis of substituted N-[3-(3-methoxyphenyl)propyl] amides as highly potent MT(2)-selective melatonin ligands. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2582-5.
• [9] 2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues: a novel class of MT2-selective melatonin receptor antagonists. J Med Chem. 2009 Feb 12;52(3):826-33.
• [10] Synthesis and structure-activity relationship of novel benzoxazole derivatives as melatonin receptor agonists. Bioorg Med Chem Lett. 2004 Jul 16;14(14):3799-802.