Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLS74AF)

• DOT Name: 5-hydroxytryptamine receptor 1D (HTR1D)
• Synonyms: 5-HT-1D; 5-HT1D; Serotonin 1D alpha receptor; 5-HT-1D-alpha; Serotonin receptor 1D
• Gene Name: HTR1D
• UniProt ID: 5HT1D_HUMAN
• PDB ID: 7.00E+32
• Pfam ID: PF00001
• Sequence:
  MSPLNQSAEGLPQEASNRSLNATETSEAWDPRTLQALKISLAVVLSVITLATVLSNAFVL
  TTILLTRKLHTPANYLIGSLATTDLLVSILVMPISIAYTITHTWNFGQILCDIWLSSDIT
  CCTASILHLCVIALDRYWAITDALEYSKRRTAGHAATMIAIVWAISICISIPPLFWRQAK
  AQEEMSDCLVNTSQISYTIYSTCGAFYIPSVLLIILYGRIYRAARNRILNPPSLYGKRFT
  TAHLITGSAGSSLCSLNSSLHEGHSHSAGSPLFFNHVKIKLADSALERKRISAARERKAT
  KILGIILGAFIICWLPFFVVSLVLPICRDSCWIHPALFDFFTWLGYLNSLINPIIYTVFN
  EEFRQAFQKIVPFRKAS
• Function: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.
• Tissue Specificity: Detected in brain neocortex and caudate nucleus (at protein level).
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Serotonergic sy.pse (hsa04726)
  Taste transduction (hsa04742)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  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
Arsenic trioxide	DM61TA4	Approved	5-hydroxytryptamine receptor 1D (HTR1D) decreases the response to substance of Arsenic trioxide.	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Serotonin	DMOFCRY	Investigative	5-hydroxytryptamine receptor 1D (HTR1D) affects the abundance of Serotonin.	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of 5-hydroxytryptamine receptor 1D (HTR1D).	[1]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of 5-hydroxytryptamine receptor 1D (HTR1D).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of 5-hydroxytryptamine receptor 1D (HTR1D).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of 5-hydroxytryptamine receptor 1D (HTR1D).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 5-hydroxytryptamine receptor 1D (HTR1D).	[5]

References

• [1] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [2] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [3] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [4] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [5] Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.
• [6] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.
• [7] Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels. Hum Genet. 2007 Apr;121(2):243-56. doi: 10.1007/s00439-006-0301-3. Epub 2007 Jan 3.