Target Information

Target General Infomation
Target ID
T79062
Former ID
TTDR00157
Target Name
5-hydroxytryptamine 7 receptor
Gene Name
HTR7
Synonyms
5-HT-7; 5-HT-X; 5-HT7 receptor; 5HT7; Serotonin receptor; Serotonin receptor 7; HTR7
Target Type
Clinical Trial
Disease Major depressive disorder [ICD9: 296.2, 296.3, 710.0; ICD10: F32, F33, M32]
Psychiatric disorder [ICD9: 290-319; ICD10: F01-F99]
Schizophrenia [ICD9: 295; ICD10: F20]
Sleep disorders [ICD9: 307.4, 327, 780.5; ICD10: F51, G47]
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.
BioChemical Class
GPCR rhodopsin
Target Validation
T79062
UniProt ID
P34969
Sequence
MMDVNSSGRPDLYGHLRSFLLPEVGRGLPDLSPDGGADPVAGSWAPHLLSEVTASPAPTW
DAPPDNASGCGEQINYGRVEKVVIGSILTLITLLTIAGNCLVVISVCFVKKLRQPSNYLI
VSLALADLSVAVAVMPFVSVTDLIGGKWIFGHFFCNVFIAMDVMCCTASIMTLCVISIDR
YLGITRPLTYPVRQNGKCMAKMILSVWLLSASITLPPLFGWAQNVNDDKVCLISQDFGYT
IYSTAVAFYIPMSVMLFMYYQIYKAARKSAAKHKFPGFPRVEPDSVIALNGIVKLQKEVE
ECANLSRLLKHERKNISIFKREQKAATTLGIIVGAFTVCWLPFFLLSTARPFICGTSCSC
IPLWVERTFLWLGYANSLINPFIYAFFNRDLRTTYRSLLQCQYRNINRKLSAAGMHEALK
LAERPERPEFVLRACTRRVLLRPEKRPPVSVWVLQSPDHHNWLADKMLTTVEKKVMIHD
Drugs and Mode of Action
Drug(s) JNJ-18038683 Drug Info Phase 2 Major depressive disorder [1], [2]
ATI-9242 Drug Info Discontinued in Phase 2 Schizophrenia [3]
SB-269970 Drug Info Terminated Sleep disorders [4], [5]
Agonist (+)-LSD Drug Info [6]
1-naphthylpiperazine Drug Info [7]
2-MPP Drug Info [8]
5-CT Drug Info [9]
AS-19 Drug Info [10]
bufotenine Drug Info [9]
dipropyl-5-CT Drug Info [11]
DM-1451 Drug Info [12]
E55888 Drug Info [13]
EMDT Drug Info [14]
LP-12 Drug Info [15]
LP-211 Drug Info [16]
LP-44 Drug Info [15]
m-chlorophenylpiperazine Drug Info [8]
OPC 4392 Drug Info [12]
TFMPP Drug Info [8]
[125I]LSD Drug Info [17]
[3H]5-CT Drug Info [18]
[3H]5-HT Drug Info [7]
[3H]LSD Drug Info [19]
Inhibitor (+/-)-nantenine Drug Info [20]
(2-biphenyl-3-yl-ethyl)-dimethyl-amine Drug Info [21]
(R)-8-phenyl-N,N-dipropylchroman-3-amine Drug Info [22]
1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine Drug Info [23]
1-Naphthalen-1-yl-piperazine Drug Info [24]
2-(1-o-tolyl-1H-pyrrol-3-yl)ethanamine Drug Info [21]
2-(2'-methyl-biphenyl-3-yl)-ethylamine Drug Info [21]
2-(2-Bromophenoxy)-N,N-dimethylethanamine Drug Info [22]
2-(2-Bromophenylthio)-N,N-dimethylethanamine Drug Info [22]
2-(Biphenyl-2-yloxy)-N,N-dimethylethanamine Drug Info [22]
2-(Biphenyl-2-ylthio)-N,N-dimethylethanamine Drug Info [22]
2-[1-(2-Chloro-phenyl)-1H-pyrrol-2-yl]-ethylamine Drug Info [25]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one Drug Info [26]
5,6-dichloro-3,4-dihydroquinazolin-2-amine Drug Info [27]
5-chloro-3,4-dihydroquinazolin-2-amine Drug Info [27]
5-chloro-4-ethyl-3,4-dihydroquinazolin-2-amine Drug Info [27]
5-chloro-4-methyl-3,4-dihydroquinazolin-2-amine Drug Info [27]
8-methoxy-4-methyl-3,4-dihydroquinazolin-2-amine Drug Info [27]
Disulergine Drug Info [24]
FALCARINDIOL Drug Info [28]
IMPERATORIN Drug Info [28]
MESULERGINE Drug Info [29]
METHIOTHEPIN Drug Info [30]
N,N-dimethyl-2-(2'-methylbiphenyl-3-yl)ethanamine Drug Info [22]
P-hydroxyphenethyl trans-ferulate Drug Info [28]
SB-258719 Drug Info [24]
SB-258741 Drug Info [24]
SB-271046 Drug Info [31]
SB-656104 Drug Info [24]
SEROTONIN Drug Info [32]
SPIPERONE Drug Info [24]
UCM-5600 Drug Info [29]
WAY-208466 Drug Info [33]
WAY-466 Drug Info [34]
Antagonist 2-bromo-LSD Drug Info [9]
cyamemazine Drug Info [35]
dihydroergocryptine Drug Info [9]
DR-4004 Drug Info [24]
fluperlapine Drug Info [36]
JNJ-18038683 Drug Info [37]
metergoline Drug Info [7]
MPDT Drug Info [14]
pirenperone Drug Info [11]
SB 269970-A Drug Info [38]
SB 656104-A Drug Info [38]
[3H]SB269970 Drug Info [18]
Modulator ATI-9242 Drug Info [39]
SB-269970 Drug Info
SEL-73 Drug Info [40]
Modulator (allosteric modulator) oleamide Drug Info [41]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Ras signaling pathway
Calcium signaling pathway
Neuroactive ligand-receptor interaction
Serotonergic synapse
PANTHER Pathway Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway
PathWhiz Pathway Excitatory Neural Signalling Through 5-HTR 7 and Serotonin
Reactome Serotonin receptors
G alpha (s) signalling events
WikiPathways Serotonin Receptor 4/6/7 and NR3C Signaling
Monoamine GPCRs
GPCRs, Class A Rhodopsin-like
GPCR ligand binding
GPCR downstream signaling
GPCRs, Other
References
REF 1ClinicalTrials.gov (NCT00566202) A Safety and Effectiveness Study of JNJ-18038683 in Patients With Moderate to Severe Depression. U.S. National Institutes of Health.
REF 2(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: 8432).
REF 3Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028165)
REF 4(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: 3233).
REF 5Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017732)
REF 6Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8547-51.
REF 7Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. J Biol Chem. 1993 Nov 5;268(31):23422-6.
REF 8Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. J Biol Chem. 1993 Aug 25;268(24):18200-4.
REF 9Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase. Mol Pharmacol. 1993 Aug;44(2):229-36.
REF 10Discovery of aryl-biphenyl-2-ylmethylpiperazines as novel scaffolds for 5-HT(7) ligands and role of the aromatic substituents in binding to the target receptor. Bioorg Med Chem. 2013 May 1;21(9):2568-76.
REF 11Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7b). Br J Pharmacol. 1997 Sep;122(1):126-32.
REF 12Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes. Neuropsychopharmacology. 1999 Jun;20(6):612-27.
REF 135-HT7 receptor activation inhibits mechanical hypersensitivity secondary to capsaicin sensitization in mice. Pain. 2009 Feb;141(3):239-47.
REF 142-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J Med Chem. 2000 Mar 9;43(5):1011-8.
REF 15Structure-activity relationship study on N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamides, a class of 5-HT7 receptor agents. 2. J Med Chem. 2007 Aug 23;50(17):4214-21. Epub 2007 Jul 25.
REF 16J Med Chem. 2008 Sep 25;51(18):5813-22.Structural modifications of N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamides: influence on lipophilicity and 5-HT7 receptor activity. Part III.
REF 17A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. Neuron. 1993 Sep;11(3):449-58.
REF 18[(3)H]-SB-269970--A selective antagonist radioligand for 5-HT(7) receptors. Br J Pharmacol. 2000 May;130(2):409-17.
REF 19Human serotonin 5-HT7 receptor: cloning and pharmacological characterisation of two receptor variants. FEBS Lett. 1997 Aug 25;413(3):489-94.
REF 20Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. Epub 2009 Nov 20.Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine.
REF 21Bioorg Med Chem Lett. 2007 Jun 1;17(11):3018-22. Epub 2007 Mar 23.Novel aminoethylbiphenyls as 5-HT7 receptor ligands.
REF 22Bioorg Med Chem. 2010 Mar 1;18(5):1958-67. Epub 2010 Jan 18.SAR studies on new bis-aryls 5-HT7 ligands: Synthesis and molecular modeling.
REF 23Bioorg Med Chem. 2007 Nov 1;15(21):6659-66. Epub 2007 Aug 15.The synthesis and biological activity of pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine.
REF 24J Med Chem. 2003 Jul 3;46(14):2795-812.Higher-end serotonin receptors: 5-HT(5), 5-HT(6), and 5-HT(7).
REF 25Bioorg Med Chem Lett. 2005 Aug 15;15(16):3753-7.Phenylpyrroles, a new chemolibrary virtual screening class of 5-HT7 receptor ligands.
REF 26J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential.
REF 27Bioorg Med Chem Lett. 2008 Jan 1;18(1):256-61. Epub 2007 Oct 30.Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: structure-activity relationship elucidation.
REF 28J Nat Prod. 2006 Apr;69(4):536-41.Serotonergic activity-guided phytochemical investigation of the roots of Angelica sinensis.
REF 29J Med Chem. 2009 Apr 23;52(8):2384-92.Synthesis of new serotonin 5-HT7 receptor ligands. Determinants of 5-HT7/5-HT1A receptor selectivity.
REF 30Bioorg Med Chem. 2008 Mar 1;16(5):2570-8. Epub 2007 Nov 22.Novel quinazolinone derivatives as 5-HT7 receptor ligands.
REF 31Bioorg Med Chem Lett. 2008 Jan 15;18(2):738-43. Epub 2007 Nov 17.Discovery of 3-aryl-3-methyl-1H-quinoline-2,4-diones as a new class of selective 5-HT6 receptor antagonists.
REF 32J Med Chem. 2008 Jul 24;51(14):4150-69. Epub 2008 Jun 28.Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity.
REF 33Bioorg Med Chem. 2009 Jul 15;17(14):5153-63. Epub 2009 May 29.Novel 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines are potent 5-HT(6) agonists.
REF 34J Med Chem. 2005 Jan 27;48(2):353-6.Discovery of 5-arylsulfonamido-3-(pyrrolidin-2-ylmethyl)-1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists.
REF 35Affinity of cyamemazine, an anxiolytic antipsychotic drug, for human recombinant dopamine vs. serotonin receptor subtypes. Biochem Pharmacol. 2003 Feb 1;65(3):435-40.
REF 36Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10.
REF 37Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity. Front Behav Neurosci. 2015 Jan 15;8:453.
REF 385-HT7 receptors. Curr Drug Targets CNS Neurol Disord. 2004 Feb;3(1):81-90.
REF 39Pharmacological characteristics of ATI-9242, a Novel Atypical Antipsychotic. FASEB J, April, 2010, 24(Meeting Abstract Supplement),773.12.
REF 40(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. (Target id: 12).
REF 41Allosteric regulation by oleamide of the binding properties of 5-hydroxytryptamine7 receptors. Biochem Pharmacol. 1999 Dec 1;58(11):1807-13.

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