Target Information
Target General Infomation | |||||
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Target ID |
T07806
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Former ID |
TTDS00099
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Target Name |
5-hydroxytryptamine 1B receptor
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Gene Name |
HTR1B
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Synonyms |
5-HT-1B; 5-HT-1D-beta; 5-HT1B receptor; S12; Serotonin 1D beta receptor; Serotonin receptor; Serotonin receptor 1B; HTR1B
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Target Type |
Successful
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Disease | Aggressive non-hodgkin's lymphoma [ICD9: 200, 201, 202, 202.8, 208.9; ICD10: C81, C81-C86, C82-C85, C91-C95] | ||||
Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42] | |||||
Chronic schizophrenics [ICD9: 295; ICD10: F20] | |||||
Major depressive disorder [ICD9: 296.2, 296.3, 710.0; ICD10: F32, F33, M32] | |||||
Mood disorder [ICD10: F30-F39] | |||||
Migraine [ICD9: 346; ICD10: G43] | |||||
Migraine headaches [ICD9: 346; ICD10: G43] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Psychotic disorders [ICD9: 290-299; ICD10: F20-F29] | |||||
Severe mood disorders [ICD9: 296; ICD10: F30-F39] | |||||
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, such as lysergic acid diethylamide (LSD). 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. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
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BioChemical Class |
GPCR rhodopsin
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Target Validation |
T07806
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UniProt ID | |||||
Sequence |
MEEPGAQCAPPPPAGSETWVPQANLSSAPSQNCSAKDYIYQDSISLPWKVLLVMLLALIT
LATTLSNAFVIATVYRTRKLHTPANYLIASLAVTDLLVSILVMPISTMYTVTGRWTLGQV VCDFWLSSDITCCTASILHLCVIALDRYWAITDAVEYSAKRTPKRAAVMIALVWVFSISI SLPPFFWRQAKAEEEVSECVVNTDHILYTVYSTVGAFYFPTLLLIALYGRIYVEARSRIL KQTPNRTGKRLTRAQLITDSPGSTSSVTSINSRVPDVPSESGSPVYVNQVKVRVSDALLE KKKLMAARERKATKTLGIILGAFIVCWLPFFIISLVMPICKDACWFHLAIFDFFTWLGYL NSLINPIIYTMSNEDFKQAFHKLIRFKCTS |
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Drugs and Mode of Action | |||||
Drug(s) | Dihydroergotamine nasal | Drug Info | Approved | Migraine | [1] |
Eletriptan | Drug Info | Approved | Migraine | [2], [3] | |
Fluphenazine | Drug Info | Approved | Psychotic disorders | [4], [5] | |
Frovatriptan | Drug Info | Approved | Migraine headaches | [2], [6] | |
Naratriptan | Drug Info | Approved | Migraine headaches | [7], [2] | |
Prolixin decanoate | Drug Info | Approved | Chronic schizophrenics | [8] | |
Zolmitriptan | Drug Info | Approved | Migraine | [9], [10] | |
Eltoprazine | Drug Info | Phase 2 | Aggressive non-hodgkin's lymphoma | [11] | |
NXN-188 | Drug Info | Phase 2 | Migraine | [12] | |
[N-methyl-3H(3)]AZ-10419369 | Drug Info | Phase 1 | Mood disorder | [13], [14] | |
Donitriptan | Drug Info | Preclinical | Migraine | [15], [16] | |
Elzasonan hydrochloride | Drug Info | Discontinued in Phase 2 | Severe mood disorders | [17] | |
IS-159 | Drug Info | Discontinued in Phase 2 | Migraine | [18] | |
Anpirtoline | Drug Info | Terminated | Pain | [19] | |
AZD-1134 | Drug Info | Terminated | Anxiety disorder | [20] | |
CGS-12066B | Drug Info | Terminated | Anxiety disorder | [21], [22] | |
F-12682 | Drug Info | Terminated | Major depressive disorder | [23] | |
GR-127935 | Drug Info | Terminated | Major depressive disorder | [24], [25] | |
L-775606 | Drug Info | Terminated | Discovery agent | [26], [27] | |
VR-147 | Drug Info | Terminated | Migraine | [28] | |
Inhibitor | (+/-)-nantenine | Drug Info | [29] | ||
1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine | Drug Info | [30] | |||
1-(7-Methoxy-naphthalen-2-yl)-piperazine | Drug Info | [31] | |||
1-Naphthalen-2-yl-piperazine | Drug Info | [31] | |||
2-(5-Thiophen-2-yl-1H-indol-3-yl)-ethylamine | Drug Info | [32] | |||
5-amino-3-(N-methylpiperidin-4-yl)-1H-indole | Drug Info | [33] | |||
5-Ethyl-3-(2-pyrrolidin-1-yl-ethyl)-1H-indole | Drug Info | [34] | |||
5-Isopropyl-3-(2-pyrrolidin-1-yl-ethyl)-1H-indole | Drug Info | [34] | |||
A-987306 | Drug Info | [35] | |||
L-747201 | Drug Info | [36] | |||
L-775606 | Drug Info | [36] | |||
SEROTONIN | Drug Info | [35] | |||
WAY-466 | Drug Info | [37] | |||
[2-(5-Ethyl-1H-indol-3-yl)-ethyl]-dimethyl-amine | Drug Info | [34] | |||
Antagonist | (R)-flurocarazolol | Drug Info | [38] | ||
(S)-flurocarazolol | Drug Info | [38] | |||
5-OH-DPAT | Drug Info | [39] | |||
9-OH-risperidone | Drug Info | [40] | |||
AZD-1134 | Drug Info | [41], [1] | |||
F-12682 | Drug Info | [42], [1] | |||
GR55562 | Drug Info | [43] | |||
metergoline | Drug Info | [44] | |||
SB 224289 | Drug Info | [43] | |||
SB 272183 | Drug Info | [45] | |||
SB 649915 | Drug Info | [46] | |||
SB 714786 | Drug Info | [46] | |||
SB236057 | Drug Info | [47] | |||
[3H]GR 125,743 | Drug Info | [48] | |||
[N-methyl-3H(3)]AZ-10419369 | Drug Info | [49], [1] | |||
Agonist | 1-naphthylpiperazine | Drug Info | [44] | ||
2-methyl-5-HT | Drug Info | [50] | |||
5-(nonyloxy)-tryptamine | Drug Info | [51] | |||
5-CT | Drug Info | [39] | |||
7-methoxy-1-naphthylpiperazine | Drug Info | [31] | |||
BRL-15572 | Drug Info | [52] | |||
CP-94,253 | Drug Info | [53] | |||
dipropyl-5-CT | Drug Info | [50] | |||
Eltoprazine | Drug Info | [54], [1] | |||
L-772,405 | Drug Info | [55] | |||
lysergol | Drug Info | [44] | |||
Naratriptan | Drug Info | [56] | |||
SB 216641 | Drug Info | [52] | |||
SB 236057-A | Drug Info | [57] | |||
TFMPP | Drug Info | [44] | |||
[11C]AZ10419369 | Drug Info | [58] | |||
[125I]GTI | Drug Info | [59] | |||
[3H]8-OH-DPAT | Drug Info | [60] | |||
[3H]alniditan | Drug Info | [61] | |||
[3H]eletriptan | Drug Info | [62] | |||
[3H]sumatriptan | Drug Info | [62] | |||
Modulator | Anpirtoline | Drug Info | [19] | ||
CGS-12066B | Drug Info | ||||
Dihydroergotamine nasal | Drug Info | [61] | |||
Donitriptan | Drug Info | ||||
Eletriptan | Drug Info | [63] | |||
Elzasonan hydrochloride | Drug Info | ||||
Fluphenazine | Drug Info | [63] | |||
Frovatriptan | Drug Info | [63] | |||
GR-127935 | Drug Info | ||||
IS-159 | Drug Info | ||||
NXN-188 | Drug Info | ||||
Prolixin decanoate | Drug Info | [63] | |||
VR-147 | Drug Info | [64], [1] | |||
Zolmitriptan | Drug Info | [63] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | cAMP signaling pathway | ||||
Neuroactive ligand-receptor interaction | |||||
Serotonergic synapse | |||||
PANTHER Pathway | Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | ||||
5HT1 type receptor mediated signaling pathway | |||||
Reactome | Serotonin receptors | ||||
G alpha (i) signalling events | |||||
WikiPathways | Serotonin HTR1 Group and FOS Pathway | ||||
Monoamine GPCRs | |||||
GPCRs, Class A Rhodopsin-like | |||||
GPCR ligand binding | |||||
GPCR downstream signaling | |||||
References | |||||
REF 1 | Sustained pain relief with dihydroergotamine in migraine is potentially due to persistent binding to 5-HT1B and 5-HT1D receptors. . The Journal of Headache and Pain 201314(Suppl 1):P75. | ||||
REF 2 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20. | ||||
REF 3 | (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: 40). | ||||
REF 4 | The antipsychotic drug, fluphenazine, effectively reverses mechanical allodynia in rat models of neuropathic pain. Psychopharmacology (Berl). 2008 Jan;195(4):559-68. Epub 2007 Sep 23. | ||||
REF 5 | (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: 204). | ||||
REF 6 | (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: 7191). | ||||
REF 7 | (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: 45). | ||||
REF 8 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 016727. | ||||
REF 9 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020768. | ||||
REF 10 | (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: 60). | ||||
REF 11 | ClinicalTrials.gov (NCT01266174) Effects of Eltoprazine on Cognitive Impairment Associated With Schizophrenia (CIAS) in Adults. U.S. National Institutes of Health. | ||||
REF 12 | ClinicalTrials.gov (NCT00920686) Study of NXN 188 for the Treatment of Migraine With Aura. U.S. National Institutes of Health. | ||||
REF 13 | ClinicalTrials.gov (NCT01085123) Determine Central 5-HT1B Receptor Occupancy of ZOMIG Rapimelt (Zolmitriptan) in Healthy Male Volunteers. U.S. National Institutes of Health. | ||||
REF 14 | (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: 3219). | ||||
REF 15 | (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: 39). | ||||
REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012002) | ||||
REF 17 | Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2. | ||||
REF 18 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005786) | ||||
REF 19 | Effects of anpirtoline on regional serotonin synthesis in the rat brain: an autoradiographic study. Nucl Med Biol. 2006 Apr;33(3):325-32. Epub 2006 Mar 9. | ||||
REF 20 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017898) | ||||
REF 21 | (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: 109). | ||||
REF 22 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006033) | ||||
REF 23 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010898) | ||||
REF 24 | (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: 14). | ||||
REF 25 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002743) | ||||
REF 26 | (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: 114). | ||||
REF 27 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009132) | ||||
REF 28 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023937) | ||||
REF 29 | 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 30 | 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 31 | J Med Chem. 1997 Nov 21;40(24):3974-8.5-HT1B receptor antagonist properties of novel arylpiperazide derivatives of 1-naphthylpiperazine. | ||||
REF 32 | Bioorg Med Chem Lett. 2000 May 1;10(9):903-5.5-Thienyltryptamine derivatives as serotonin 5-HT1B/1D receptor agonists: potential treatments for migraine. | ||||
REF 33 | J Med Chem. 2008 Jun 26;51(12):3609-16. Epub 2008 May 29.Designing selective, high affinity ligands of 5-HT1D receptor by covalent dimerization of 5-HT1F ligands derived from 4-fluoro-N-[3-(1-methyl-4-piperidinyl)-1H-indol-5-yl]benzamide. | ||||
REF 34 | Bioorg Med Chem Lett. 2000 Aug 7;10(15):1707-9.5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor agonists. | ||||
REF 35 | 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 36 | J Med Chem. 1997 Oct 24;40(22):3501-3.Selective, orally active 5-HT1D receptor agonists as potential antimigraine agents. | ||||
REF 37 | J 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 38 | The in vitro pharmacology of the beta-adrenergic receptor pet ligand (s)-fluorocarazolol reveals high affinity for cloned beta-adrenergic receptors and moderate affinity for the human 5-HT1A receptor. Psychopharmacology (Berl). 2001 Aug;157(1):111-4. | ||||
REF 39 | Mouse 5HT1B serotonin receptor: cloning, functional expression, and localization in motor control centers. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3020-4. | ||||
REF 40 | Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. | ||||
REF 41 | N-methyl-3H3AZ10419369 binding to the 5-HT1B receptor: in vitro characterization and in vivo receptor occupancy. J Pharmacol Exp Ther. 2009 Jul;330(1):342-51. | ||||
REF 42 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010898) | ||||
REF 43 | 5-hydroxytryptamine receptors mediating contraction in human small muscular pulmonary arteries: importance of the 5-HT1B receptor. Br J Pharmacol. 1999 Oct;128(3):730-4. | ||||
REF 44 | Two amino acid differences in the sixth transmembrane domain are partially responsible for the pharmacological differences between the 5-HT1D beta and 5-HT1E 5-hydroxytryptamine receptors. J Neurochem. 1996 Nov;67(5):2096-103. | ||||
REF 45 | SB-272183, a selective 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptor antagonist in native tissue. Br J Pharmacol. 2001 Jul;133(6):797-806. | ||||
REF 46 | Discovery of the first potent, selective 5-hydroxytryptamine1D receptor antagonist. J Med Chem. 2005 May 19;48(10):3478-80. | ||||
REF 47 | SB-236057, a selective 5-HT1B receptor inverse agonist, blocks the 5-HT human terminal autoreceptor. Eur J Pharmacol. 1999 Jun 30;375(1-3):359-65. | ||||
REF 48 | Serotonin 5-HT1B and 5-HT1D receptors form homodimers when expressed alone and heterodimers when co-expressed. FEBS Lett. 1999 Jul 30;456(1):63-7. | ||||
REF 49 | 5-HT1B and other related serotonergic proteins are altered in APPswe mutation. Neurosci Lett. 2015 May 6;594:137-43. | ||||
REF 50 | Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3630-4. | ||||
REF 51 | Identification of an amino acid residue important for binding of methiothepin and sumatriptan to the human 5-HT(1B) receptor. Eur J Pharmacol. 1999 Sep 10;380(2-3):171-81. | ||||
REF 52 | 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 53 | Anxiogenic-like effect of serotonin(1B) receptor stimulation in the rat elevated plus-maze. Pharmacol Biochem Behav. 2002 Apr;71(4):581-7. | ||||
REF 54 | Clinical pipeline report, company report or official report of Jazz Pharmaceuticals. | ||||
REF 55 | 3-[3-(Piperidin-1-yl)propyl]indoles as highly selective h5-HT(1D) receptor agonists. J Med Chem. 1999 Dec 2;42(24):4981-5001. | ||||
REF 56 | Triptans in pregnancy. Ther Drug Monit. 2008 Feb;30(1):5-9. | ||||
REF 57 | SB-236057-A: a selective 5-HT1B receptor inverse agonist. CNS Drug Rev. 2001 Winter;7(4):433-44. | ||||
REF 58 | Quantitative analysis of [11C]AZ10419369 binding to 5-HT1B receptors in human brain. J Cereb Blood Flow Metab. 2011 Jan;31(1):113-23. | ||||
REF 59 | Autoradiographic characterisation and localisation of 5-HT1D compared to 5-HT1B binding sites in rat brain. Naunyn Schmiedebergs Arch Pharmacol. 1993 Jun;347(6):569-82. | ||||
REF 60 | Actions of roxindole at recombinant human dopamine D2, D3 and D4 and serotonin 5-HT1A, 5-HT1B and 5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1999 Jun;359(6):447-53. | ||||
REF 61 | Br J Pharmacol. 1998 Apr;123(8):1655-65.Agonistic properties of alniditan, sumatriptan and dihydroergotamine on human 5-HT1B and 5-HT1D receptors expressed in various mammalian cell lines. | ||||
REF 62 | Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics of [3H]eletriptan binding at human 5-HT1B and 5-HT1D receptors. Eur J Pharmacol. 1999 Mar 5;368(2-3):259-68. | ||||
REF 63 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | ||||
REF 64 | US patent application no. 2010,0112,050, Dosage form for insertion into the mouth. |
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