Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYYV8JK)

• DOT Name: Melatonin receptor type 1A (MTNR1A)
• Synonyms: Mel-1A-R; Mel1a receptor
• Gene Name: MTNR1A
• UniProt ID: MTR1A_HUMAN
• PDB ID: 6ME2; 6ME3; 6ME4; 6ME5; 7DB6; 7VGY; 7VGZ
• Pfam ID: PF00001
• Sequence:
  MQGNGSALPNASQPVLRGDGARPSWLASALACVLIFTIVVDILGNLLVILSVYRNKKLRN
  AGNIFVVSLAVADLVVAIYPYPLVLMSIFNNGWNLGYLHCQVSGFLMGLSVIGSIFNITG
  IAINRYCYICHSLKYDKLYSSKNSLCYVLLIWLLTLAAVLPNLRAGTLQYDPRIYSCTFA
  QSVSSAYTIAVVVFHFLVPMIIVIFCYLRIWILVLQVRQRVKPDRKPKLKPQDFRNFVTM
  FVVFVLFAICWAPLNFIGLAVASDPASMVPRIPEWLFVASYYMAYFNSCLNAIIYGLLNQ
  NFRKEYRRIIVSLCTARVFFVDSSNDVADRVKWKPSPLMTNNNVVKVDSV
• Function: High affinity receptor for melatonin. 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.
• Tissue Specificity: Expressed in hypophyseal pars tuberalis and hypothalamic suprachiasmatic nuclei (SCN). Hippocampus.
• 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 DOT

4 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the binding of Melatonin receptor type 1A (MTNR1A).	[1]
Agomelatine	DMXYA5K	Withdrawn from market	Agomelatine affects the binding of Melatonin receptor type 1A (MTNR1A).	[3]
CHRYSOERIOL	DM96ECL	Investigative	CHRYSOERIOL affects the binding of Melatonin receptor type 1A (MTNR1A).	[1]
4P-PDOT	DMEMN0W	Investigative	4P-PDOT affects the binding of Melatonin receptor type 1A (MTNR1A).	[4]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Melatonin receptor type 1A (MTNR1A).	[2]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] 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.