Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8GTDDY)

• DOT Name: 5-hydroxytryptamine receptor 6 (HTR6)
• Synonyms: 5-HT-6; 5-HT6; Serotonin receptor 6
• Gene Name: HTR6
• UniProt ID: 5HT6R_HUMAN
• PDB ID: 7XTB; 7YS6; 8JLZ
• Pfam ID: PF00001
• Sequence:
  MVPEPGPTANSTPAWGAGPPSAPGGSGWVAAALCVVIALTAAANSLLIALICTQPALRNT
  SNFFLVSLFTSDLMVGLVVMPPAMLNALYGRWVLARGLCLLWTAFDVMCCSASILNLCLI
  SLDRYLLILSPLRYKLRMTPLRALALVLGAWSLAALASFLPLLLGWHELGHARPPVPGQC
  RLLASLPFVLVASGLTFFLPSGAICFTYCRILLAARKQAVQVASLTTGMASQASETLQVP
  RTPRPGVESADSRRLATKHSRKALKASLTLGILLGMFFVTWLPFFVANIVQAVCDCISPG
  LFDVLTWLGYCNSTMNPIIYPLFMRDFKRALGRFLPCPRCPRERQASLASPSLRTSHSGP
  RPGLSLQQVLPLPLPPDSDSDSDAGSGGSSGLRLTAQLLLPGEATQDPPLPTRAAAAVNF
  FNIDPAEPELRPHPLGIPTN
• Function: This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs. Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity. Is an activator of TOR signaling.
• Tissue Specificity: Expressed in several human brain regions, most prominently in the caudate nucleus.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Serotonergic sy.pse (hsa04726)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Serotonin receptors (R-HSA-390666)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	5-hydroxytryptamine receptor 6 (HTR6) increases the response to substance of Methamphetamine.	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Clozapine	DMFC71L	Approved	Clozapine affects the binding of 5-hydroxytryptamine receptor 6 (HTR6).	[1]
Olanzapine	DMPFN6Y	Approved	Olanzapine affects the binding of 5-hydroxytryptamine receptor 6 (HTR6).	[1]
LYSERGIC ACID DIETHYLAMIDE	DMACMLO	Withdrawn from market	LYSERGIC ACID DIETHYLAMIDE affects the binding of 5-hydroxytryptamine receptor 6 (HTR6).	[3]
SB 258585	DM2QJKZ	Investigative	SB 258585 affects the binding of 5-hydroxytryptamine receptor 6 (HTR6).	[5]

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 5-hydroxytryptamine receptor 6 (HTR6).	[2]

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of 5-hydroxytryptamine receptor 6 (HTR6).	[4]

References

• [1] No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation. Pharmacogenomics J. 2007 Aug;7(4):275-81. doi: 10.1038/sj.tpj.6500418. Epub 2006 Sep 19.
• [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] N'-(arylsulfonyl)pyrazoline-1-carboxamidines as novel, neutral 5-hydroxytryptamine 6 receptor (5-HT?R) antagonists with unique structural features. J Med Chem. 2011 Oct 27;54(20):7030-54. doi: 10.1021/jm200466r. Epub 2011 Sep 26.
• [4] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [5] 5-HT6 receptor binding sites in schizophrenia and following antipsychotic drug administration: autoradiographic studies with [125I]SB-258585. Synapse. 2002 Sep 1;45(3):191-9.
• [6] Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population. Drug Alcohol Depend. 2011 Jan 1;113(1):1-7. doi: 10.1016/j.drugalcdep.2010.06.021. Epub 2010 Aug 11.