Target Information

Target General Information

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Target ID

T79062 (Former ID: TTDR00157)

Target Name

5-HT 7 receptor (HTR7)

Synonyms

Serotonin receptor 7; 5HT7; 5-hydroxytryptamine receptor 7; 5-HT7 receptor; 5-HT7; 5-HT-X; 5-HT-7

Gene Name

HTR7

Target Type

Clinical trial target

[1]

Disease

[+] 7 Target-related Diseases

Depression [ICD-11: 6A70-6A7Z]

Mild neurocognitive disorder [ICD-11: 6D71]

Alzheimer disease [ICD-11: 8A20]

Attention deficit hyperactivity disorder [ICD-11: 6A05]

Bipolar disorder [ICD-11: 6A60]

Parkinsonism [ICD-11: 8A00]

Schizophrenia [ICD-11: 6A20]

Function

The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. 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.

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BioChemical Class

GPCR rhodopsin

UniProt ID

5HT7R_HUMAN

Sequence

MMDVNSSGRPDLYGHLRSFLLPEVGRGLPDLSPDGGADPVAGSWAPHLLSEVTASPAPTW
DAPPDNASGCGEQINYGRVEKVVIGSILTLITLLTIAGNCLVVISVCFVKKLRQPSNYLI
VSLALADLSVAVAVMPFVSVTDLIGGKWIFGHFFCNVFIAMDVMCCTASIMTLCVISIDR
YLGITRPLTYPVRQNGKCMAKMILSVWLLSASITLPPLFGWAQNVNDDKVCLISQDFGYT
IYSTAVAFYIPMSVMLFMYYQIYKAARKSAAKHKFPGFPRVEPDSVIALNGIVKLQKEVE
ECANLSRLLKHERKNISIFKREQKAATTLGIIVGAFTVCWLPFFLLSTARPFICGTSCSC
IPLWVERTFLWLGYANSLINPFIYAFFNRDLRTTYRSLLQCQYRNINRKLSAAGMHEALK
LAERPERPEFVLRACTRRVLLRPEKRPPVSVWVLQSPDHHNWLADKMLTTVEKKVMIHD

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

HIT2.0 ID

T63IUV

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 4 Clinical Trial Drugs

AVN-101

Drug Info

Phase 2

Cognitive impairment

[2]

JNJ-18038683

Drug Info

Phase 2

Major depressive disorder

[3], [4]

RP5063

Drug Info

Phase 2

Schizophrenia

[5]

ATI-9242

Drug Info

Phase 1

Schizophrenia

[6]

Patented Agent(s)

[+] 2 Patented Agents

PMID30124346-Compound-13TABLE4

Drug Info

Patented

Attention deficit hyperactivity disorder

[7]

PMID30124346-Compound-34TABLE4

Drug Info

Patented

Attention deficit hyperactivity disorder

[7]

Discontinued Drug(s)

[+] 1 Discontinued Drugs

SB-269970

Drug Info

Terminated

Sleep-wake disorder

[8], [9]

Mode of Action

[+] 7 Modes of Action

Antagonist

[+] 11 Antagonist drugs

AVN-101

Drug Info

[10]

JNJ-18038683

Drug Info

[11]

2-bromo-LSD

Drug Info

[22]

cyamemazine

Drug Info

[27]

dihydroergocryptine

Drug Info

[22]

DR-4004

Drug Info

[21]

fluperlapine

Drug Info

[34]

MPDT

Drug Info

[31]

N-methyl-Pip-F-homoF-vinyl sulfonyl phenyl (N-methyl-Pip-F-hF-VS phi)

Drug Info

[39]

pirenperone

Drug Info

[28]

SB 269970-A

Drug Info

[39]

Partial agonist

[+] 1 Partial agonist drugs

RP5063

Drug Info

[6]

Modulator

[+] 3 Modulator drugs

ATI-9242

Drug Info

[12]

SB-269970

Drug Info

[14], [15]

SEL-73

Drug Info

[41]

Inhibitor

[+] 35 Inhibitor drugs

4-oxadiazole derivative 1

Drug Info

[13]

Carbamide derivative 2

Drug Info

[13]

(+/-)-nantenine

Drug Info

[16]

(2-biphenyl-3-yl-ethyl)-dimethyl-amine

Drug Info

[17]

(R)-8-phenyl-N,N-dipropylchroman-3-amine

Drug Info

[18]

1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine

Drug Info

[20]

2-(1-o-tolyl-1H-pyrrol-3-yl)ethanamine

Drug Info

[17]

2-(2'-methyl-biphenyl-3-yl)-ethylamine

Drug Info

[17]

2-(2-Bromophenoxy)-N,N-dimethylethanamine

Drug Info

[18]

2-(2-Bromophenylthio)-N,N-dimethylethanamine

Drug Info

[18]

2-(Biphenyl-2-yloxy)-N,N-dimethylethanamine

Drug Info

[18]

2-(Biphenyl-2-ylthio)-N,N-dimethylethanamine

Drug Info

[18]

2-[1-(2-Chloro-phenyl)-1H-pyrrol-2-yl]-ethylamine

Drug Info

[23]

4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one

Drug Info

[24]

5,6-dichloro-3,4-dihydroquinazolin-2-amine

Drug Info

[25]

5-chloro-3,4-dihydroquinazolin-2-amine

Drug Info

[25]

5-chloro-4-ethyl-3,4-dihydroquinazolin-2-amine

Drug Info

[25]

5-chloro-4-methyl-3,4-dihydroquinazolin-2-amine

Drug Info

[25]

8-methoxy-4-methyl-3,4-dihydroquinazolin-2-amine

Drug Info

[25]

Disulergine

Drug Info

[21]

FALCARINDIOL

Drug Info

[33]

IMPERATORIN

Drug Info

[33]

MESULERGINE

Drug Info

[37]

METHIOTHEPIN

Drug Info

[38]

N,N-dimethyl-2-(2'-methylbiphenyl-3-yl)ethanamine

Drug Info

[18]

P-hydroxyphenethyl trans-ferulate

Drug Info

[33]

SB-258719

Drug Info

[21]

SB-258741

Drug Info

[21]

SB-271046

Drug Info

[40]

SB-656104

Drug Info

[21]

SEROTONIN

Drug Info

[42]

UCM-5600

Drug Info

[37]

WAY-208466

Drug Info

[43]

WAY-466

Drug Info

[44]

[3H]spiperone

Drug Info

[21]

Ligand

[+] 2 Ligand drugs

PMID30124346-Compound-13TABLE4

Drug Info

[7]

PMID30124346-Compound-34TABLE4

Drug Info

[7]

Agonist

[+] 19 Agonist drugs

1-(2-Methoxy-phenyl)-piperazine

Drug Info

[19]

1-naphthylpiperazine

Drug Info

[1], [21]

5-CT

Drug Info

[22]

AS-19

Drug Info

[26]

bufotenine

Drug Info

[22]

dipropyl-5-CT

Drug Info

[28]

DM-1451

Drug Info

[29]

E55888

Drug Info

[30]

EDMT

Drug Info

[31]

LP-12

Drug Info

[35]

LP-211

Drug Info

[36]

LP-44

Drug Info

[35]

m-chlorophenylpiperazine

Drug Info

[19]

OPC 4392

Drug Info

[29]

TFMPP

Drug Info

[19]

[125I]LSD

Drug Info

[45]

[3H]5-CT

Drug Info

[14]

[3H]5-HT

Drug Info

[1]

[3H]LSD

Drug Info

[46]

Modulator (allosteric modulator)

[+] 1 Modulator (allosteric modulator) drugs

Elaidoylamide

Drug Info

[32]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 4 KEGG Pathways

Ras signaling pathway

Calcium signaling pathway

Neuroactive ligand-receptor interaction

Serotonergic synapse

Panther Pathway

[+] 1 Panther Pathways

Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway

Pathwhiz Pathway

[+] 1 Pathwhiz Pathways

Excitatory Neural Signalling Through 5-HTR 7 and Serotonin

Reactome

[+] 2 Reactome Pathways

Serotonin receptors

G alpha (s) signalling events

WikiPathways

[+] 6 WikiPathways

Serotonin Receptor 4/6/7 and NR3C Signaling

Monoamine GPCRs

GPCRs, Class A Rhodopsin-like

GPCR ligand binding

GPCR downstream signaling

GPCRs, Other

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. J Biol Chem. 1993 Nov 5;268(31):23422-6.

REF 2

Clinical pipeline report, company report or official report of Avineuro.

REF 3

URL: 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 4

ClinicalTrials.gov (NCT00566202) A Safety and Effectiveness Study of JNJ-18038683 in Patients With Moderate to Severe Depression. U.S. National Institutes of Health.

REF 5

ClinicalTrials.gov (NCT01490086) RP5063 in Subjects With Schizophrenia or Schizoaffective Disorder. U.S. National Institutes of Health.

REF 6

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 7

5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.

REF 8

REF 9

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017732)

REF 10

AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders. J Alzheimers Dis. 2016 May 25;53(2):583-620.

REF 11

Selective 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 12

Pharmacological characteristics of ATI-9242, a Novel Atypical Antipsychotic. FASEB J, April, 2010, 24(Meeting Abstract Supplement),773.12.

REF 13

Acyltransferase inhibitors: a patent review (2010-present).Expert Opin Ther Pat. 2015 Feb;25(2):145-58.

REF 14

[(3)H]-SB-269970--A selective antagonist radioligand for 5-HT(7) receptors. Br J Pharmacol. 2000 May;130(2):409-17.

REF 15

Characterization of SB-269970-A, a selective 5-HT(7) receptor antagonist. Br J Pharmacol. 2000 Jun;130(3):539-48.

REF 16

Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.

REF 17

Novel aminoethylbiphenyls as 5-HT7 receptor ligands. Bioorg Med Chem Lett. 2007 Jun 1;17(11):3018-22.

REF 18

SAR studies on new bis-aryls 5-HT7 ligands: Synthesis and molecular modeling. Bioorg Med Chem. 2010 Mar 1;18(5):1958-67.

REF 19

Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. J Biol Chem. 1993 Aug 25;268(24):18200-4.

REF 20

The synthesis and biological activity of pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine. Bioorg Med Chem. 2007 Nov 1;15(21):6659-66.

REF 21

Higher-end serotonin receptors: 5-HT(5), 5-HT(6), and 5-HT(7). J Med Chem. 2003 Jul 3;46(14):2795-812.

REF 22

Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase. Mol Pharmacol. 1993 Aug;44(2):229-36.

REF 23

Phenylpyrroles, a new chemolibrary virtual screening class of 5-HT7 receptor ligands. Bioorg Med Chem Lett. 2005 Aug 15;15(16):3753-7.

REF 24

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 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.

REF 25

Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: structure-activity relationship elucidation. Bioorg Med Chem Lett. 2008 Jan 1;18(1):256-61.

REF 26

Discovery 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 27

Affinity of cyamemazine, an anxiolytic antipsychotic drug, for human recombinant dopamine vs. serotonin receptor subtypes. Biochem Pharmacol. 2003 Feb 1;65(3):435-40.

REF 28

Cloning, 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 29

Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes. Neuropsychopharmacology. 1999 Jun;20(6):612-27.

REF 30

5-HT7 receptor activation inhibits mechanical hypersensitivity secondary to capsaicin sensitization in mice. Pain. 2009 Feb;141(3):239-47.

REF 31

2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J Med Chem. 2000 Mar 9;43(5):1011-8.

REF 32

Allosteric regulation by oleamide of the binding properties of 5-hydroxytryptamine7 receptors. Biochem Pharmacol. 1999 Dec 1;58(11):1807-13.

REF 33

Serotonergic activity-guided phytochemical investigation of the roots of Angelica sinensis. J Nat Prod. 2006 Apr;69(4):536-41.

REF 34

Binding 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 35

Structure-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.

REF 36

Structural modifications of N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamides: influence on lipophilicity and 5-HT7 receptor act... J Med Chem. 2008 Sep 25;51(18):5813-22.

REF 37

Synthesis of new serotonin 5-HT7 receptor ligands. Determinants of 5-HT7/5-HT1A receptor selectivity. J Med Chem. 2009 Apr 23;52(8):2384-92.

REF 38

Novel quinazolinone derivatives as 5-HT7 receptor ligands. Bioorg Med Chem. 2008 Mar 1;16(5):2570-8.

REF 39

5-HT7 receptors. Curr Drug Targets CNS Neurol Disord. 2004 Feb;3(1):81-90.

REF 40

Discovery of 3-aryl-3-methyl-1H-quinoline-2,4-diones as a new class of selective 5-HT6 receptor antagonists. Bioorg Med Chem Lett. 2008 Jan 15;18(2):738-43.

REF 41

REF 42

Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69.

REF 43

Novel 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines are potent 5-HT(6) agonists. Bioorg Med Chem. 2009 Jul 15;17(14):5153-63.

REF 44

Discovery of 5-arylsulfonamido-3-(pyrrolidin-2-ylmethyl)-1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists. J Med Chem. 2005 Jan 27;48(2):353-6.

REF 45

A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. Neuron. 1993 Sep;11(3):449-58.

REF 46

Human serotonin 5-HT7 receptor: cloning and pharmacological characterisation of two receptor variants. FEBS Lett. 1997 Aug 25;413(3):489-94.

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