Target Information
Target General Information | Top | |||||
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Target ID |
T79062
(Former ID: TTDR00157)
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Target Name |
5-HT 7 receptor (HTR7)
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Synonyms |
Serotonin receptor 7; 5HT7; 5-hydroxytryptamine receptor 7; 5-HT7 receptor; 5-HT7; 5-HT-X; 5-HT-7
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Gene Name |
HTR7
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 7 Target-related Diseases | + | ||||
1 | Depression [ICD-11: 6A70-6A7Z] | |||||
2 | Mild neurocognitive disorder [ICD-11: 6D71] | |||||
3 | Alzheimer disease [ICD-11: 8A20] | |||||
4 | Attention deficit hyperactivity disorder [ICD-11: 6A05] | |||||
5 | Bipolar disorder [ICD-11: 6A60] | |||||
6 | Parkinsonism [ICD-11: 8A00] | |||||
7 | 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
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UniProt ID | ||||||
Sequence |
MMDVNSSGRPDLYGHLRSFLLPEVGRGLPDLSPDGGADPVAGSWAPHLLSEVTASPAPTW
DAPPDNASGCGEQINYGRVEKVVIGSILTLITLLTIAGNCLVVISVCFVKKLRQPSNYLI VSLALADLSVAVAVMPFVSVTDLIGGKWIFGHFFCNVFIAMDVMCCTASIMTLCVISIDR YLGITRPLTYPVRQNGKCMAKMILSVWLLSASITLPPLFGWAQNVNDDKVCLISQDFGYT IYSTAVAFYIPMSVMLFMYYQIYKAARKSAAKHKFPGFPRVEPDSVIALNGIVKLQKEVE ECANLSRLLKHERKNISIFKREQKAATTLGIIVGAFTVCWLPFFLLSTARPFICGTSCSC IPLWVERTFLWLGYANSLINPFIYAFFNRDLRTTYRSLLQCQYRNINRKLSAAGMHEALK LAERPERPEFVLRACTRRVLLRPEKRPPVSVWVLQSPDHHNWLADKMLTTVEKKVMIHD Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T63IUV |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
1 | AVN-101 | Drug Info | Phase 2 | Cognitive impairment | [2] | |
2 | JNJ-18038683 | Drug Info | Phase 2 | Major depressive disorder | [3], [4] | |
3 | RP5063 | Drug Info | Phase 2 | Schizophrenia | [5] | |
4 | ATI-9242 | Drug Info | Phase 1 | Schizophrenia | [6] | |
Patented Agent(s) | [+] 2 Patented Agents | + | ||||
1 | PMID30124346-Compound-13TABLE4 | Drug Info | Patented | Attention deficit hyperactivity disorder | [7] | |
2 | PMID30124346-Compound-34TABLE4 | Drug Info | Patented | Attention deficit hyperactivity disorder | [7] | |
Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | SB-269970 | Drug Info | Terminated | Sleep-wake disorder | [8], [9] | |
Mode of Action | [+] 7 Modes of Action | + | ||||
Antagonist | [+] 11 Antagonist drugs | + | ||||
1 | AVN-101 | Drug Info | [10] | |||
2 | JNJ-18038683 | Drug Info | [11] | |||
3 | 2-bromo-LSD | Drug Info | [22] | |||
4 | cyamemazine | Drug Info | [27] | |||
5 | dihydroergocryptine | Drug Info | [22] | |||
6 | DR-4004 | Drug Info | [21] | |||
7 | fluperlapine | Drug Info | [34] | |||
8 | MPDT | Drug Info | [31] | |||
9 | N-methyl-Pip-F-homoF-vinyl sulfonyl phenyl (N-methyl-Pip-F-hF-VS phi) | Drug Info | [39] | |||
10 | pirenperone | Drug Info | [28] | |||
11 | SB 269970-A | Drug Info | [39] | |||
Partial agonist | [+] 1 Partial agonist drugs | + | ||||
1 | RP5063 | Drug Info | [6] | |||
Modulator | [+] 3 Modulator drugs | + | ||||
1 | ATI-9242 | Drug Info | [12] | |||
2 | SB-269970 | Drug Info | [14], [15] | |||
3 | SEL-73 | Drug Info | [41] | |||
Inhibitor | [+] 35 Inhibitor drugs | + | ||||
1 | 4-oxadiazole derivative 1 | Drug Info | [13] | |||
2 | Carbamide derivative 2 | Drug Info | [13] | |||
3 | (+/-)-nantenine | Drug Info | [16] | |||
4 | (2-biphenyl-3-yl-ethyl)-dimethyl-amine | Drug Info | [17] | |||
5 | (R)-8-phenyl-N,N-dipropylchroman-3-amine | Drug Info | [18] | |||
6 | 1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine | Drug Info | [20] | |||
7 | 2-(1-o-tolyl-1H-pyrrol-3-yl)ethanamine | Drug Info | [17] | |||
8 | 2-(2'-methyl-biphenyl-3-yl)-ethylamine | Drug Info | [17] | |||
9 | 2-(2-Bromophenoxy)-N,N-dimethylethanamine | Drug Info | [18] | |||
10 | 2-(2-Bromophenylthio)-N,N-dimethylethanamine | Drug Info | [18] | |||
11 | 2-(Biphenyl-2-yloxy)-N,N-dimethylethanamine | Drug Info | [18] | |||
12 | 2-(Biphenyl-2-ylthio)-N,N-dimethylethanamine | Drug Info | [18] | |||
13 | 2-[1-(2-Chloro-phenyl)-1H-pyrrol-2-yl]-ethylamine | Drug Info | [23] | |||
14 | 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [24] | |||
15 | 5,6-dichloro-3,4-dihydroquinazolin-2-amine | Drug Info | [25] | |||
16 | 5-chloro-3,4-dihydroquinazolin-2-amine | Drug Info | [25] | |||
17 | 5-chloro-4-ethyl-3,4-dihydroquinazolin-2-amine | Drug Info | [25] | |||
18 | 5-chloro-4-methyl-3,4-dihydroquinazolin-2-amine | Drug Info | [25] | |||
19 | 8-methoxy-4-methyl-3,4-dihydroquinazolin-2-amine | Drug Info | [25] | |||
20 | Disulergine | Drug Info | [21] | |||
21 | FALCARINDIOL | Drug Info | [33] | |||
22 | IMPERATORIN | Drug Info | [33] | |||
23 | MESULERGINE | Drug Info | [37] | |||
24 | METHIOTHEPIN | Drug Info | [38] | |||
25 | N,N-dimethyl-2-(2'-methylbiphenyl-3-yl)ethanamine | Drug Info | [18] | |||
26 | P-hydroxyphenethyl trans-ferulate | Drug Info | [33] | |||
27 | SB-258719 | Drug Info | [21] | |||
28 | SB-258741 | Drug Info | [21] | |||
29 | SB-271046 | Drug Info | [40] | |||
30 | SB-656104 | Drug Info | [21] | |||
31 | SEROTONIN | Drug Info | [42] | |||
32 | UCM-5600 | Drug Info | [37] | |||
33 | WAY-208466 | Drug Info | [43] | |||
34 | WAY-466 | Drug Info | [44] | |||
35 | [3H]spiperone | Drug Info | [21] | |||
Ligand | [+] 2 Ligand drugs | + | ||||
1 | PMID30124346-Compound-13TABLE4 | Drug Info | [7] | |||
2 | PMID30124346-Compound-34TABLE4 | Drug Info | [7] | |||
Agonist | [+] 19 Agonist drugs | + | ||||
1 | 1-(2-Methoxy-phenyl)-piperazine | Drug Info | [19] | |||
2 | 1-naphthylpiperazine | Drug Info | [1], [21] | |||
3 | 5-CT | Drug Info | [22] | |||
4 | AS-19 | Drug Info | [26] | |||
5 | bufotenine | Drug Info | [22] | |||
6 | dipropyl-5-CT | Drug Info | [28] | |||
7 | DM-1451 | Drug Info | [29] | |||
8 | E55888 | Drug Info | [30] | |||
9 | EDMT | Drug Info | [31] | |||
10 | LP-12 | Drug Info | [35] | |||
11 | LP-211 | Drug Info | [36] | |||
12 | LP-44 | Drug Info | [35] | |||
13 | m-chlorophenylpiperazine | Drug Info | [19] | |||
14 | OPC 4392 | Drug Info | [29] | |||
15 | TFMPP | Drug Info | [19] | |||
16 | [125I]LSD | Drug Info | [45] | |||
17 | [3H]5-CT | Drug Info | [14] | |||
18 | [3H]5-HT | Drug Info | [1] | |||
19 | [3H]LSD | Drug Info | [46] | |||
Modulator (allosteric modulator) | [+] 1 Modulator (allosteric modulator) drugs | + | ||||
1 | Elaidoylamide | Drug Info | [32] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"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 | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
1 | Ras signaling pathway | |||||
2 | Calcium signaling pathway | |||||
3 | Neuroactive ligand-receptor interaction | |||||
4 | Serotonergic synapse | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Excitatory Neural Signalling Through 5-HTR 7 and Serotonin | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | Serotonin receptors | |||||
2 | G alpha (s) signalling events | |||||
WikiPathways | [+] 6 WikiPathways | + | ||||
1 | Serotonin Receptor 4/6/7 and NR3C Signaling | |||||
2 | Monoamine GPCRs | |||||
3 | GPCRs, Class A Rhodopsin-like | |||||
4 | GPCR ligand binding | |||||
5 | GPCR downstream signaling | |||||
6 | GPCRs, Other |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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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 | 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: 3233). | |||||
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 | 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. (Target id: 12). | |||||
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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