Target Information
Target General Infomation | |||||
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Target ID |
T41580
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Former ID |
TTDC00293
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Target Name |
Alpha-2B adrenergic receptor
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Gene Name |
ADRA2B
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Synonyms |
Alpha-2B adrenoceptor; Alpha-2B adrenoreceptor; Subtype C2; ADRA2B
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Target Type |
Successful
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Disease | Alcohol use disorders [ICD9: 303; ICD10: F10.2] | ||||
Heart arrhythmia [ICD10: I47-I49] | |||||
Hypertension [ICD9: 401; ICD10: I10-I16] | |||||
Neuropathic pain [ICD9: 356.0, 356.8; ICD10: G64, G90.0] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Function |
Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.
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BioChemical Class |
GPCR rhodopsin
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Target Validation |
T41580
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UniProt ID | |||||
Sequence |
MDHQDPYSVQATAAIAAAITFLILFTIFGNALVILAVLTSRSLRAPQNLFLVSLAAADIL
VATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY NSKRTPRRIKCIILTVWLIAAVISLPPLIYKGDQGPQPRGRPQCKLNQEAWYILASSIGS FFAPCLIMILVYLRIYLIAKRSNRRGPRAKGGPGQGESKQPRPDHGGALASAKLPALASV ASAREVNGHSKSTGEKEEGETPEDTGTRALPPSWAALPNSGQGQKEGVCGASPEDEAEEE EEEEEEEEECEPQAVPVSPASACSPPLQQPQGSRVLATLRGQVLLGRGVGAIGGQWWRRR AQLTREKRFTFVLAVVIGVFVLCWFPFFFSYSLGAICPKHCKVPHGLFQFFFWIGYCNSS LNPVIYTIFNQDFRRAFRRILCRPWTQTAW |
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Drugs and Mode of Action | |||||
Drug(s) | MOXONIDINE | Drug Info | Approved | Alcohol use disorders | [526626] |
AGN-199981 | Drug Info | Phase 2 | Neuropathic pain | [536374] | |
MEDETOMIDINE | Drug Info | Phase 2 | Pain | [529347] | |
INDORAMIN | Drug Info | Withdrawn from market | Hypertension | [468125], [551871] | |
MAZAPERTINE | Drug Info | Discontinued in Phase 2 | Discovery agent | [545274] | |
A-80426 | Drug Info | Terminated | Discovery agent | [546043] | |
SK&F-104078 | Drug Info | Terminated | Discovery agent | [544626] | |
SNAP-5089 | Drug Info | Terminated | Heart arrhythmia | [468115], [546179] | |
WB-4101 | Drug Info | Terminated | Discovery agent | [468117], [545656] | |
Inhibitor | (+/-)-nantenine | Drug Info | [530558] | ||
(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanol | Drug Info | [525507] | |||
(2-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
(3-Ethyl-indol-1-yl)-propyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
(3-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
(R)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [534195] | |||
(S)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [534195] | |||
1',2',3',6'-Tetrahydro-[2,4']bipyridinyl | Drug Info | [533509] | |||
1,2,3,4,4a,5,10,10a-Octahydro-benzo[g]quinoline | Drug Info | [534719] | |||
1,2,3,4,5,6-Hexahydro-benzo[c]azocine | Drug Info | [534195] | |||
1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-ol | Drug Info | [534531] | |||
1,2,3,4-Tetrahydro-isoquinolin-7-ol | Drug Info | [534531] | |||
1,2,3,4-Tetrahydro-pyrazino[1,2-a]indole | Drug Info | [526994] | |||
1,2,3,4-tetrahydroisoquinoline | Drug Info | [528403] | |||
1-(3-Fluoro-pyridin-2-yl)-4-methyl-piperazine | Drug Info | [533509] | |||
1-(pyridin-2-yl)piperazine | Drug Info | [533509] | |||
2,3,4,5-Tetrahydro-1H-benzo[c]azepine | Drug Info | [534195] | |||
2,3,4,5-Tetrahydro-1H-benzo[e][1,4]diazepine | Drug Info | [534195] | |||
2,3,4,5-Tetrahydro-benzo[f][1,4]oxazepine | Drug Info | [534195] | |||
2,3-Dihydro-1H-isoindole | Drug Info | [534195] | |||
2-BFi | Drug Info | [525733] | |||
3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [527365] | |||
3-Methoxymethyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [525507] | |||
3-Methyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [534195] | |||
4-(1-Naphthalen-1-yl-ethyl)-1H-imidazole | Drug Info | [533805] | |||
4-(4-Methyl-indan-1-yl)-1H-imidazole | Drug Info | [534467] | |||
4-Benzo[b]thiophen-4-yl-1H-imidazole | Drug Info | [525720] | |||
5-Aminomethyl-naphthalen-2-ol | Drug Info | [534531] | |||
6,7,8,9-Tetrahydro-5-thia-8-aza-benzocycloheptene | Drug Info | [534195] | |||
7-Methoxy-2,3,4,9-tetrahydro-1H-beta-carboline | Drug Info | [526918] | |||
8-Methoxy-1,2,3,4-tetrahydro-benzo[h]isoquinoline | Drug Info | [534531] | |||
A-80426 | Drug Info | [527481] | |||
Butyl-indol-1-yl-pyridin-4-yl-amine | Drug Info | [534087] | |||
C-(6-Methoxy-naphthalen-1-yl)-methylamine | Drug Info | [534531] | |||
C-Naphthalen-1-yl-methylamine | Drug Info | [534531] | |||
Ethyl-indol-1-yl-pyridin-4-yl-amine | Drug Info | [534087] | |||
GNF-PF-2857 | Drug Info | [528472] | |||
GNF-PF-3427 | Drug Info | [528472] | |||
GNF-PF-3878 | Drug Info | [528472] | |||
Indol-1-yl-methyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
Indol-1-yl-prop-2-ynyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
Indol-1-yl-propyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
Indol-1-yl-pyridin-4-yl-amine | Drug Info | [534087] | |||
INDORAMIN | Drug Info | [533682] | |||
MAZAPERTINE | Drug Info | [533800] | |||
MEDETOMIDINE | Drug Info | [533805] | |||
METHYLNORADRENALINE | Drug Info | [533545] | |||
MEZILAMINE | Drug Info | [533406] | |||
MOXONIDINE | Drug Info | [534128] | |||
PIPEROXAN | Drug Info | [533545] | |||
R-226161 | Drug Info | [528772] | |||
RX-821002 | Drug Info | [533375] | |||
S-34324 | Drug Info | [527481] | |||
SK&F-104078 | Drug Info | [533682] | |||
SK&F-64139 | Drug Info | [528403] | |||
SNAP-5089 | Drug Info | [525611] | |||
SNAP-5150 | Drug Info | [525611] | |||
TRACIZOLINE | Drug Info | [526918] | |||
TRAMAZOLINE | Drug Info | [533545] | |||
TRYPTOLINE | Drug Info | [526918] | |||
WB-4101 | Drug Info | [533545] | |||
Agonist | AGN-199981 | Drug Info | [536374] | ||
xylazine | Drug Info | [534634] | |||
Antagonist | imiloxan | Drug Info | [530335] | ||
spiroxatrine | Drug Info | [533843] | |||
[3H]MK-912 | Drug Info | [533843] | |||
[3H]rauwolscine | Drug Info | [526770] | |||
[3H]RX821002 | Drug Info | [533799] | |||
Pathways | |||||
KEGG Pathway | cGMP-PKG signaling pathway | ||||
Neuroactive ligand-receptor interaction | |||||
PANTHER Pathway | Alpha adrenergic receptor signaling pathway | ||||
Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | |||||
Reactome | Adrenoceptors | ||||
Adrenaline signalling through Alpha-2 adrenergic receptor | |||||
G alpha (i) signalling events | |||||
G alpha (z) signalling events | |||||
WikiPathways | Monoamine GPCRs | ||||
GPCRs, Class A Rhodopsin-like | |||||
Platelet Aggregation (Plug Formation) | |||||
GPCR ligand binding | |||||
GPCR downstream signaling | |||||
References | |||||
Ref 468115 | (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: 498). | ||||
Ref 468117 | (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: 499). | ||||
Ref 468125 | (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: 501). | ||||
Ref 526626 | The role of I(1)-imidazoline and alpha(2)-adrenergic receptors in the modulation of glucose metabolism in the spontaneously hypertensive obese rat model of metabolic syndrome X. J Pharmacol Exp Ther.2003 Aug;306(2):646-57. Epub 2003 May 19. | ||||
Ref 529347 | Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves. Am J Vet Res. 2008 Mar;69(3):319-29. | ||||
Ref 544626 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000354) | ||||
Ref 545274 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002662) | ||||
Ref 545656 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004048) | ||||
Ref 546043 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006017) | ||||
Ref 525507 | J Med Chem. 1999 Jun 3;42(11):1982-90.3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines display remarkable potency and selectivity as inhibitors of phenylethanolamine N-methyltransferase versus the alpha2-adrenoceptor. | ||||
Ref 525611 | Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.Design and synthesis of novel dihydropyridine alpha-1a antagonists. | ||||
Ref 525720 | J Med Chem. 2000 Mar 9;43(5):765-8.alpha(2) Adrenoceptor agonists as potential analgesic agents. 2. Discovery of 4-(4-Imidazo)-1,3-dimethyl-6,7-dihydrothianaphthene [corrected] as a high-affinity ligand for the alpha(2D) adrenergic receptor. | ||||
Ref 525733 | Bioorg Med Chem Lett. 2000 Mar 20;10(6):605-7.Probes for imidazoline binding sites: synthesis and evaluation of a selective, irreversible I2 ligand. | ||||
Ref 526770 | Pharmacological characteristics of alpha 2-adrenergic receptors: comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning. Mol Pharmacol. 1992 Jul;42(1):1-5. | ||||
Ref 526918 | Bioorg Med Chem Lett. 2004 Jan 19;14(2):527-9.Binding of an imidazopyridoindole at imidazoline I2 receptors. | ||||
Ref 526994 | Bioorg Med Chem Lett. 2004 Feb 23;14(4):1003-5.Pyrazino[1,2-a]indoles as novel high-affinity and selective imidazoline I(2) receptor ligands. | ||||
Ref 527365 | J Med Chem. 2005 Jan 13;48(1):134-40.3-hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline inhibitors of phenylethanolamine N-methyltransferase that display remarkable potency and selectivity. | ||||
Ref 527481 | J Med Chem. 2005 Mar 24;48(6):2054-71.Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking activity. | ||||
Ref 528403 | J Med Chem. 2006 Sep 7;49(18):5424-33.Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamineN-methyltransferase. | ||||
Ref 528472 | J Med Chem. 2006 Oct 19;49(21):6351-63.Structure-activity relationship of quinoline derivatives as potent and selective alpha(2C)-adrenoceptor antagonists. | ||||
Ref 528772 | Bioorg Med Chem. 2007 Jun 1;15(11):3649-60. Epub 2007 Mar 21.Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-adrenoceptor antagonism. | ||||
Ref 530335 | Assessment of imiloxan as a selective alpha 2B-adrenoceptor antagonist. Br J Pharmacol. 1990 Mar;99(3):560-4. | ||||
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 533375 | J Med Chem. 1986 Oct;29(10):2000-3.Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists. | ||||
Ref 533406 | J Med Chem. 1986 Aug;29(8):1394-8.4-Amino-6-chloro-2-piperazinopyrimidines with selective affinity for alpha 2-adrenoceptors. | ||||
Ref 533509 | J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines. | ||||
Ref 533545 | J Med Chem. 1982 Dec;25(12):1389-401.alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs. | ||||
Ref 533682 | J Med Chem. 1995 Sep 1;38(18):3415-44.Alpha- and beta-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. | ||||
Ref 533799 | Further characterization of human alpha 2-adrenoceptor subtypes: [3H]RX821002 binding and definition of additional selective drugs. Eur J Pharmacol. 1994 Jan 24;252(1):43-9. | ||||
Ref 533800 | J Med Chem. 1994 Apr 15;37(8):1060-2.A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. | ||||
Ref 533805 | J Med Chem. 1994 Jul 22;37(15):2328-33.A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic receptors. | ||||
Ref 533843 | The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors. J Pharmacol Exp Ther. 1994 Dec;271(3):1558-65. | ||||
Ref 534087 | J Med Chem. 1996 Jan 19;39(2):570-81.Synthesis and structure-activity relationships of N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine) and related analogs as potential therapeutic agents for Alzheimer's disease. | ||||
Ref 534128 | J Med Chem. 1996 Mar 15;39(6):1193-5.Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. | ||||
Ref 534195 | J Med Chem. 1996 Aug 30;39(18):3539-46.Effect of ring size or an additional heteroatom on the potency and selectivity of bicyclic benzylamine-type inhibitors of phenylethanolamine N-methyltransferase. | ||||
Ref 534467 | J Med Chem. 1997 Sep 12;40(19):3014-24.Medetomidine analogs as alpha 2-adrenergic ligands. 3. Synthesis and biological evaluation of a new series of medetomidine analogs and their potential binding interactions with alpha 2-adrenoceptors involving a "methyl pocket". | ||||
Ref 534531 | J Med Chem. 1997 Dec 5;40(25):3997-4005.Examination of the role of the acidic hydrogen in imparting selectivity of 7-(aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) toward inhibition of phenylethanolamine N-methyltransferase vs the alpha 2-adrenoceptor. | ||||
Ref 534634 | Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding. Biochem Pharmacol. 1998 Apr 1;55(7):1035-43. |
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