Target Information
Target General Infomation | |||||
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Target ID |
T31204
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Former ID |
TTDS00104
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Target Name |
5-hydroxytryptamine 2B receptor
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Gene Name |
HTR2B
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Synonyms |
5-HT 2B; 5-HT-2B; Serotonin receptor; Serotonin receptor 2B; HTR2B
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Target Type |
Successful
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Disease | Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42] | ||||
Coronary heart disease [ICD9: 414; ICD10: I25.1] | |||||
Congestive heart failure [ICD9: 428; ICD10: I50] | |||||
Depression; Cerebral infarction [ICD9:311; ICD10: F30-F39, I63] | |||||
Irritable bowel syndrome [ICD9: 564.1, 787.91; ICD10: A09, K58, K59.1] | |||||
Migraine [ICD9: 346; ICD10: G43] | |||||
Psychotic disorders [ICD9: 290-299; ICD10: F20-F29] | |||||
Psychoses [ICD9: 290-299; ICD10: F20-F29] | |||||
Pulmonary arterial hypertension [ICD9: 416; ICD10: I27.0, I27.2] | |||||
Function |
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and 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. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down- stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5- hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine.
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BioChemical Class |
GPCR rhodopsin
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Target Validation |
T31204
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UniProt ID | |||||
Sequence |
MALSYRVSELQSTIPEHILQSTFVHVISSNWSGLQTESIPEEMKQIVEEQGNKLHWAALL
ILMVIIPTIGGNTLVILAVSLEKKLQYATNYFLMSLAVADLLVGLFVMPIALLTIMFEAM WPLPLVLCPAWLFLDVLFSTASIMHLCAISVDRYIAIKKPIQANQYNSRATAFIKITVVW LISIGIAIPVPIKGIETDVDNPNNITCVLTKERFGDFMLFGSLAAFFTPLAIMIVTYFLT IHALQKKAYLVKNKPPQRLTWLTVSTVFQRDETPCSSPEKVAMLDGSRKDKALPNSGDET LMRRTSTIGKKSVQTISNEQRASKVLGIVFFLFLLMWCPFFITNITLVLCDSCNQTTLQM LLEIFVWIGYVSSGVNPLVYTLFNKTFRDAFGRYITCNYRATKSVKTLRKRSSKIYFRNP MAENSKFFKKHGIRNGINPAMYQSPMRLRSSTIQSSSIILLDTLLLTENEGDKTEEQVSY V |
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Drugs and Mode of Action | |||||
Drug(s) | Minaprine | Drug Info | Approved | Depression; Cerebral infarction | [536164], [551871] |
Triflupromazine | Drug Info | Approved | Psychoses | [467669], [538443] | |
PRX-08066 | Drug Info | Phase 2 | Pulmonary arterial hypertension | [536294] | |
Vabicaserin | Drug Info | Phase 2 | Psychotic disorders | [522459] | |
FENDILINE | Drug Info | Withdrawn from market | Coronary heart disease | [533443] | |
Ritanserin | Drug Info | Discontinued in Phase 3 | Anxiety disorder | [543335], [544590] | |
MT-500 | Drug Info | Discontinued in Phase 1 | Migraine | [547201] | |
LY53857 | Drug Info | Terminated | Discovery agent | [539138], [544876] | |
Ro-60-0175 | Drug Info | Terminated | Discovery agent | [539026], [546467] | |
SB 206553 | Drug Info | Terminated | Discovery agent | [539189], [546078] | |
Agonist | (+)-LSD | Drug Info | [527178] | ||
(+)-norfenfluramine | Drug Info | [525929] | |||
(-)-norfenfluramine | Drug Info | [525929] | |||
2-methyl-5-HT | Drug Info | [534042] | |||
3,4-Methylenedioxymethamphetamine | Drug Info | [551382] | |||
5-CT | Drug Info | [534042] | |||
AL-37350A | Drug Info | [526713] | |||
alpha-methyl-5-HT | Drug Info | [527238] | |||
BRL-15572 | Drug Info | [534475] | |||
BW723C86 | Drug Info | [526719] | |||
dihydroergocryptine | Drug Info | [532279] | |||
m-chlorophenylpiperazine | Drug Info | [534042] | |||
norfenfluramine | Drug Info | [525929] | |||
Org 12962 | Drug Info | [527178] | |||
SB 216641 | Drug Info | [534475] | |||
TFMPP | Drug Info | [534042] | |||
[125I]DOI | Drug Info | [543921] | |||
[3H]5-HT | Drug Info | [534042] | |||
[3H]LSD | Drug Info | [526621] | |||
Inhibitor | (+/-)-nantenine | Drug Info | [530558] | ||
(2S)-1-(6-methoxy-1H-indazol-1-yl)propan-2-amine | Drug Info | [527952] | |||
(5-methoxy-1H-indol-3-yl)methanamine | Drug Info | [531223] | |||
1-((R)-2-aminopropyl)-1H-indazol-6-ol | Drug Info | [527952] | |||
1-((S)-2-aminopropyl)-1H-indazol-6-ol | Drug Info | [527952] | |||
1-((S)-2-aminopropyl)-7-chloro-1H-indazol-6-ol | Drug Info | [527952] | |||
1-((S)-2-aminopropyl)-7-fluoro-1H-indazol-6-ol | Drug Info | [527952] | |||
1-((S)-2-aminopropyl)-7-iodo-1H-indazol-6-ol | Drug Info | [527952] | |||
1-((S)-2-aminopropyl)-7-methyl-1H-indazol-6-ol | Drug Info | [527952] | |||
1-(2-aminoethyl)-1H-indazol-6-ol | Drug Info | [527952] | |||
1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine | Drug Info | [529013] | |||
1-Butyl-3-(2-dimethylamino-ethyl)-1H-indol-4-ol | Drug Info | [527668] | |||
2-(5-Methoxy-1H-indol-3-yl)-1-methyl-ethylamine | Drug Info | [527952] | |||
3-(2-Amino-propyl)-1H-indol-5-ol | Drug Info | [527952] | |||
3-(2-Dimethylamino-ethyl)-1-methyl-1H-indol-4-ol | Drug Info | [527668] | |||
3-(2-Dimethylamino-ethyl)-1H-indol-6-ol | Drug Info | [527668] | |||
3-(2-Dimethylamino-propyl)-1H-indol-4-ol | Drug Info | [527668] | |||
3-(2-Pyrrolidin-1-yl-ethyl)-1H-indol-4-ol | Drug Info | [527668] | |||
3-(3-Dimethylamino-propyl)-1H-indol-4-ol | Drug Info | [527668] | |||
3-Dimethylaminomethyl-1-methyl-1H-indol-4-ol | Drug Info | [527668] | |||
3-Dimethylaminomethyl-1H-indol-4-ol | Drug Info | [527668] | |||
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [531079] | |||
5-MEO-DMT | Drug Info | [527952] | |||
6,7-dichloro-2,3,4,5-tetrahydro-1H-3-benzazepine | Drug Info | [529221] | |||
6-Fluoromelatonin | Drug Info | [531223] | |||
7,8,9,10-tetrahydro-6H-furo-[2,3-g][3]benzazepine | Drug Info | [529221] | |||
7,8,9,10-tetrahydro-6H-furo-[3,2-g][3]benzazepine | Drug Info | [529221] | |||
A-987306 | Drug Info | [529789] | |||
ADRENOGLOMERULOTROPIN | Drug Info | [531223] | |||
ADS-103253 | Drug Info | [528581] | |||
ADS-103274 | Drug Info | [528581] | |||
CHLOROPHENYLPIPERAZINE | Drug Info | [530589] | |||
FENDILINE | Drug Info | [531223] | |||
Racemic DOI | Drug Info | [529789] | |||
Ro-60-0175 | Drug Info | [527833] | |||
SEROTONIN | Drug Info | [527833] | |||
VER-2692 | Drug Info | [527833] | |||
VER-3323 | Drug Info | [527037] | |||
VER-5384 | Drug Info | [527037] | |||
VER-5593 | Drug Info | [527037] | |||
YM-348 | Drug Info | [529221] | |||
[2-(4-Fluoro-1H-indol-3-yl)-ethyl]-dimethyl-amine | Drug Info | [527668] | |||
Antagonist | 1-naphthylpiperazine | Drug Info | [534042] | ||
EGIS-7625 | Drug Info | [527053] | |||
LY53857 | Drug Info | [538142] | |||
LY86057 | Drug Info | [534042] | |||
metergoline | Drug Info | [527178] | |||
Minaprine | Drug Info | [535814], [536549] | |||
MT-500 | Drug Info | [551871] | |||
norfluoxetine | Drug Info | [525929] | |||
piribedil | Drug Info | [526443] | |||
PRX-08066 | Drug Info | [536294] | |||
R-1 | Drug Info | [543921] | |||
Ritanserin | Drug Info | [538142] | |||
RQ-00310941 | Drug Info | [543921] | |||
SB 204741 | Drug Info | [527178] | |||
SB 206553 | Drug Info | [535165] | |||
SB 215505 | Drug Info | [525458] | |||
SB 221284 | Drug Info | [527178] | |||
SB 228357 | Drug Info | [525730] | |||
SB 242084 | Drug Info | [534428] | |||
Small molecule 33 | Drug Info | [543921] | |||
spiramide | Drug Info | [527178] | |||
spiroxatrine | Drug Info | [534554] | |||
Triflupromazine | Drug Info | [537770] | |||
[3H]mesulergine | Drug Info | [527178] | |||
[3H]rauwolscine | Drug Info | [534554] | |||
Modulator | Vabicaserin | Drug Info | [531390] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Calcium signaling pathway | ||||
Neuroactive ligand-receptor interaction | |||||
Gap junction | |||||
Serotonergic synapse | |||||
Inflammatory mediator regulation of TRP channels | |||||
PANTHER Pathway | 5HT2 type receptor mediated signaling pathway | ||||
Reactome | Serotonin receptors | ||||
G alpha (q) signalling events | |||||
WikiPathways | Serotonin Receptor 2 and ELK-SRF/GATA4 signaling | ||||
Monoamine GPCRs | |||||
GPCRs, Class A Rhodopsin-like | |||||
Gastrin-CREB signalling pathway via PKC and MAPK | |||||
GPCR ligand binding | |||||
GPCR downstream signaling | |||||
References | |||||
Ref 467669 | (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: 4330). | ||||
Ref 522459 | ClinicalTrials.gov (NCT00768612) Study Evaluating Safety and Tolerability of Vabicaserin in Patients With Sudden Worsening of Schizophrenia. U.S. National Institutes of Health. | ||||
Ref 533443 | Value of fendiline in the treatment of patients with stable angina pectoris. Pol Tyg Lek. 1987 Nov 16;42(46):1456-8. | ||||
Ref 536164 | Novel cholinesterase inhibitors as future effective drugs for the treatment of Alzheimer's disease. Expert Opin Investig Drugs. 2006 Jan;15(1):1-12. | ||||
Ref 536294 | Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19. | ||||
Ref 538443 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 011123. | ||||
Ref 539026 | (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: 166). | ||||
Ref 539138 | (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: 183). | ||||
Ref 539189 | (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: 189). | ||||
Ref 543335 | (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: 97). | ||||
Ref 544590 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000237) | ||||
Ref 544876 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001395) | ||||
Ref 546078 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006211) | ||||
Ref 546467 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008324) | ||||
Ref 525458 | Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist. Br J Pharmacol. 1999 Feb;126(3):572-4. | ||||
Ref 525730 | Biarylcarbamoylindolines are novel and selective 5-HT(2C) receptor inverse agonists: identification of 5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]- 5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a potential antidepressant/anxiolytic agent. J Med Chem. 2000 Mar 23;43(6):1123-34. | ||||
Ref 525929 | Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. 2000 Dec 5;102(23):2836-41. | ||||
Ref 526443 | Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. | ||||
Ref 526621 | Identification of the binding sites and selectivity of sarpogrelate, a novel 5-HT2 antagonist, to human 5-HT2A, 5-HT2B and 5-HT2C receptor subtypes by molecular modeling. Life Sci. 2003 May 30;73(2):193-207. | ||||
Ref 526713 | J Med Chem. 2003 Sep 11;46(19):4188-95.A novel and selective 5-HT2 receptor agonist with ocular hypotensive activity: (S)-(+)-1-(2-aminopropyl)-8,9-dihydropyrano[3,2-e]indole. | ||||
Ref 526719 | Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their possible relevance to antimigraine efficacy. Br J Pharmacol. 2003 Sep;140(2):277-84. Epub 2003 Aug 11. | ||||
Ref 527037 | Bioorg Med Chem Lett. 2004 May 3;14(9):2367-70.Indoline derivatives as 5-HT(2C) receptor agonists. | ||||
Ref 527053 | Effects of EGIS-7625, a selective and competitive 5-HT2B receptor antagonist. Cardiovasc Drugs Ther. 2003 Sep-Nov;17(5-6):427-34. | ||||
Ref 527178 | Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23. Epub 2004 Jul 30. | ||||
Ref 527238 | The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo. Br J Pharmacol. 2004 Nov;143(5):549-60. Epub 2004 Oct 4. | ||||
Ref 527668 | Bioorg Med Chem Lett. 2005 Oct 15;15(20):4555-9.SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist. | ||||
Ref 527833 | Bioorg Med Chem Lett. 2006 Feb;16(3):677-80. Epub 2005 Oct 27.Pyrrolo(iso)quinoline derivatives as 5-HT(2C) receptor agonists. | ||||
Ref 527952 | J Med Chem. 2006 Jan 12;49(1):318-28.1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity. | ||||
Ref 528581 | Bioorg Med Chem Lett. 2007 Mar 1;17(5):1403-7. Epub 2006 Dec 2.Quinazoline and benzimidazole MCH-1R antagonists. | ||||
Ref 529013 | Bioorg 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 529221 | Bioorg Med Chem. 2008 Mar 15;16(6):3309-20. Epub 2007 Dec 8.Synthesis and structure-activity relationships of a series of benzazepine derivatives as 5-HT2C receptor agonists. | ||||
Ref 529789 | J Med Chem. 2008 Nov 27;51(22):7094-8.cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia. | ||||
Ref 530558 | Bioorg 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 530589 | Bioorg Med Chem Lett. 2010 Feb 1;20(3):1128-33. Epub 2009 Dec 6.Tricyclic dihydroquinazolinones as novel 5-HT2C selective and orally efficacious anti-obesity agents. | ||||
Ref 531079 | J 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 531223 | J Med Chem. 2010 Nov 11;53(21):7573-86.Development, validation, and use of quantitative structure-activity relationship models of 5-hydroxytryptamine (2B) receptor ligands to identify novel receptor binders and putative valvulopathic compounds among common drugs. | ||||
Ref 531390 | Characterization of vabicaserin (SCA-136), a selective 5-hydroxytryptamine 2C receptor agonist. J Pharmacol Exp Ther. 2011 Jun;337(3):673-80. | ||||
Ref 532279 | Structural features for functional selectivity at serotonin receptors. Science. 2013 May 3;340(6132):615-9. | ||||
Ref 534042 | Pharmacological characteristics of the newly cloned rat 5-hydroxytryptamine2F receptor. Mol Pharmacol. 1993 Mar;43(3):419-26. | ||||
Ref 534428 | SB 242084, a selective and brain penetrant 5-HT2C receptor antagonist. Neuropharmacology. 1997 Apr-May;36(4-5):609-20. | ||||
Ref 534475 | SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):312-20. | ||||
Ref 534554 | [3H]Rauwolscine: an antagonist radioligand for the cloned human 5-hydroxytryptamine2b (5-HT2B) receptor. Naunyn Schmiedebergs Arch Pharmacol. 1998 Jan;357(1):17-24. | ||||
Ref 535165 | Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze. Braz J Med Biol Res. 2001 May;34(5):675-82. | ||||
Ref 535814 | Protective effect of minaprine against the abnormal changes of 2-deoxyglucose uptake by rat hippocampal slices induced by hypoxia/hypoglycemia. Jpn J Pharmacol. 1992 Sep;60(1):33-8. | ||||
Ref 536294 | Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19. | ||||
Ref 536549 | Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19. | ||||
Ref 537770 | Some properties of 5-hydroxytryptamine receptors in the hindquarters of the rat. Br J Pharmacol. 1979 Sep;67(1):79-85. | ||||
Ref 538142 | p-Chloroamphetamine, a serotonin-releasing drug, elicited in rats a hyperglycemia mediated by the 5-HT1A and 5-HT2B/2C receptors. Eur J Pharmacol. 1998 Oct 23;359(2-3):185-90. | ||||
Ref 543921 | (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: 7). |
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