Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT44DEWB)

• DOT Name: 5-hydroxytryptamine receptor 7 (HTR7)
• Synonyms: 5-HT-7; 5-HT7; 5-HT-X; Serotonin receptor 7
• Gene Name: HTR7
• UniProt ID: 5HT7R_HUMAN
• PDB ID: 7XTC
• Pfam ID: PF00001
• Sequence:
  MMDVNSSGRPDLYGHLRSFLLPEVGRGLPDLSPDGGADPVAGSWAPHLLSEVTASPAPTW
  DAPPDNASGCGEQINYGRVEKVVIGSILTLITLLTIAGNCLVVISVCFVKKLRQPSNYLI
  VSLALADLSVAVAVMPFVSVTDLIGGKWIFGHFFCNVFIAMDVMCCTASIMTLCVISIDR
  YLGITRPLTYPVRQNGKCMAKMILSVWLLSASITLPPLFGWAQNVNDDKVCLISQDFGYT
  IYSTAVAFYIPMSVMLFMYYQIYKAARKSAAKHKFPGFPRVEPDSVIALNGIVKLQKEVE
  ECANLSRLLKHERKNISIFKREQKAATTLGIIVGAFTVCWLPFFLLSTARPFICGTSCSC
  IPLWVERTFLWLGYANSLINPFIYAFFNRDLRTTYRSLLQCQYRNINRKLSAAGMHEALK
  LAERPERPEFVLRACTRRVLLRPEKRPPVSVWVLQSPDHHNWLADKMLTTVEKKVMIHD
• 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.
• Tissue Specificity: Isoform A is the predominant isoform in spleen, caudate and hippocampus. Isoform B is expressed at lower levels. Isoform D is a minor isoform in terms of expression.
• KEGG Pathway:
  Ras sig.ling pathway (hsa04014)
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Serotonergic sy.pse (hsa04726)
• Reactome Pathway:
  (Name not found)
  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
Simvastatin	DM30SGU	Approved	5-hydroxytryptamine receptor 7 (HTR7) increases the response to substance of Simvastatin.	[9]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
[3H]cAMP	DMZRQU7	Investigative	5-hydroxytryptamine receptor 7 (HTR7) increases the abundance of [3H]cAMP.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 5-hydroxytryptamine receptor 7 (HTR7).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of 5-hydroxytryptamine receptor 7 (HTR7).	[2]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of 5-hydroxytryptamine receptor 7 (HTR7).	[3]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of 5-hydroxytryptamine receptor 7 (HTR7).	[5]
SL65.0472	DMU5RKC	Discontinued in Phase 2	SL65.0472 affects the activity of 5-hydroxytryptamine receptor 7 (HTR7).	[7]

5 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 7 (HTR7).	[4]
Cyproheptadine	DM92AH3	Approved	Cyproheptadine affects the binding of 5-hydroxytryptamine receptor 7 (HTR7).	[4]
SB-269970	DM8WTGA	Terminated	SB-269970 affects the binding of 5-hydroxytryptamine receptor 7 (HTR7).	[4]
ICI-169369	DMQ0IOF	Terminated	ICI-169369 affects the binding of 5-hydroxytryptamine receptor 7 (HTR7).	[4]
MESULERGINE	DMKGWAH	Investigative	MESULERGINE affects the binding of 5-hydroxytryptamine receptor 7 (HTR7).	[4]

2 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 7 (HTR7).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of 5-hydroxytryptamine receptor 7 (HTR7).	[8]

References

• [1] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [4] Clozapine and other competitive antagonists reactivate risperidone-inactivated h5-HT7 receptors: radioligand binding and functional evidence for GPCR homodimer protomer interactions. Psychopharmacology (Berl). 2010 Dec;212(4):687-97. doi: 10.1007/s00213-010-2001-x. Epub 2010 Sep 9.
• [5] PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
• [6] 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.
• [7] Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Physiogenomic association of statin-related myalgia to serotonin receptors. Muscle Nerve. 2007 Sep;36(3):329-35. doi: 10.1002/mus.20871.
• [10] Presence of a 5-HT7 receptor positively coupled to adenylate cyclase activation in human granulosa-lutein cells. J Clin Endocrinol Metab. 2000 Mar;85(3):1277-86. doi: 10.1210/jcem.85.3.6448.