Target Information

Target General Information

Target ID

T41580 (Former ID: TTDC00293)

Target Name

Adrenergic receptor alpha-2B (ADRA2B)

Synonyms

Subtype C2; Alpha-2BAR; Alpha-2B adrenoreceptor; Alpha-2B adrenoceptor; Alpha-2B adrenergic receptor; Alpha-2 adrenergic receptor subtype C2; ADRA2RL1; ADRA2L1

Gene Name

ADRA2B

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Substance abuse [ICD-11: 6C40]

Function

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. Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.

Click to Show/Hide

BioChemical Class

GPCR rhodopsin

UniProt ID

ADA2B_HUMAN

Sequence

MDHQDPYSVQATAAIAAAITFLILFTIFGNALVILAVLTSRSLRAPQNLFLVSLAAADIL
VATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY
NSKRTPRRIKCIILTVWLIAAVISLPPLIYKGDQGPQPRGRPQCKLNQEAWYILASSIGS
FFAPCLIMILVYLRIYLIAKRSNRRGPRAKGGPGQGESKQPRPDHGGALASAKLPALASV
ASAREVNGHSKSTGEKEEGETPEDTGTRALPPSWAALPNSGQGQKEGVCGASPEDEAEEE
EEEEEEEEECEPQAVPVSPASACSPPLQQPQGSRVLATLRGQVLLGRGVGAIGGQWWRRR
AQLTREKRFTFVLAVVIGVFVLCWFPFFFSYSLGAICPKHCKVPHGLFQFFFWIGYCNSS
LNPVIYTIFNQDFRRAFRRILCRPWTQTAW

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

PDB

HIT2.0 ID

T03GNH

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 1 Approved Drugs

MOXONIDINE

Drug Info

Approved

Alcohol dependence

[2]

Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

AGN-199981

Drug Info

Phase 2

Neuropathic pain

[3]

MEDETOMIDINE

Drug Info

Phase 2

Pain

[4]

Discontinued Drug(s)

[+] 2 Discontinued Drugs

INDORAMIN

Drug Info

Withdrawn from market

Hypertension

[5], [6]

SNAP-5089

Drug Info

Terminated

Heart arrhythmia

[7], [8]

Mode of Action

[+] 3 Modes of Action

Inhibitor

[+] 59 Inhibitor drugs

MOXONIDINE

Drug Info

[1]

MEDETOMIDINE

Drug Info

[9]

INDORAMIN

Drug Info

[10]

MAZAPERTINE

Drug Info

[11]

A-80426

Drug Info

[12]

SK&F-104078

Drug Info

[10]

SNAP-5089

Drug Info

[13]

WB-4101

Drug Info

[14]

(+/-)-nantenine

Drug Info

[15]

(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanol

Drug Info

[16]

(2-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine

Drug Info

[17]

(3-Ethyl-indol-1-yl)-propyl-pyridin-4-yl-amine

Drug Info

[17]

(3-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine

Drug Info

[17]

(R)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline

Drug Info

[18]

(S)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline

Drug Info

[18]

1',2',3',6'-Tetrahydro-[2,4']bipyridinyl

Drug Info

[19]

1,2,3,4,4a,5,10,10a-Octahydro-benzo[g]quinoline

Drug Info

[20]

1,2,3,4,5,6-Hexahydro-benzo[c]azocine

Drug Info

[18]

1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-ol

Drug Info

[21]

1,2,3,4-Tetrahydro-isoquinolin-7-ol

Drug Info

[21]

1,2,3,4-Tetrahydro-pyrazino[1,2-a]indole

Drug Info

[22]

1,2,3,4-tetrahydroisoquinoline

Drug Info

[23]

1-(3-Fluoro-pyridin-2-yl)-4-methyl-piperazine

Drug Info

[19]

1-(pyridin-2-yl)piperazine

Drug Info

[19]

2,3,4,5-Tetrahydro-1H-benzo[c]azepine

Drug Info

[18]

2,3,4,5-Tetrahydro-1H-benzo[e][1,4]diazepine

Drug Info

[18]

2,3,4,5-Tetrahydro-benzo[f][1,4]oxazepine

Drug Info

[18]

2,3-Dihydro-1H-isoindole

Drug Info

[18]

2-BFi

Drug Info

[24]

3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinoline

Drug Info

[25]

3-Methoxymethyl-1,2,3,4-tetrahydro-isoquinoline

Drug Info

[16]

3-Methyl-1,2,3,4-tetrahydro-isoquinoline

Drug Info

[18]

4-(1-Naphthalen-1-yl-ethyl)-1H-imidazole

Drug Info

[9]

4-(4-Methyl-indan-1-yl)-1H-imidazole

Drug Info

[26]

4-Benzo[b]thiophen-4-yl-1H-imidazole

Drug Info

[27]

5-Aminomethyl-naphthalen-2-ol

Drug Info

[21]

6,7,8,9-Tetrahydro-5-thia-8-aza-benzocycloheptene

Drug Info

[18]

7-Methoxy-2,3,4,9-tetrahydro-1H-beta-carboline

Drug Info

[28]

8-Methoxy-1,2,3,4-tetrahydro-benzo[h]isoquinoline

Drug Info

[21]

Butyl-indol-1-yl-pyridin-4-yl-amine

Drug Info

[17]

C-(6-Methoxy-naphthalen-1-yl)-methylamine

Drug Info

[21]

C-Naphthalen-1-yl-methylamine

Drug Info

[21]

Ethyl-indol-1-yl-pyridin-4-yl-amine

Drug Info

[17]

GNF-PF-2857

Drug Info

[29]

GNF-PF-3878

Drug Info

[29]

Indol-1-yl-methyl-pyridin-4-yl-amine

Drug Info

[17]

Indol-1-yl-prop-2-ynyl-pyridin-4-yl-amine

Drug Info

[17]

Indol-1-yl-pyridin-4-yl-amine

Drug Info

[17]

JP1302

Drug Info

[29]

METHYLNORADRENALINE

Drug Info

[14]

MEZILAMINE

Drug Info

[31]

PIPEROXAN

Drug Info

[14]

R-226161

Drug Info

[32]

S-34324

Drug Info

[12]

SK&F-64139

Drug Info

[23]

SNAP-5150

Drug Info

[13]

TRACIZOLINE

Drug Info

[28]

Tramazoline

Drug Info

[14]

TRYPTOLINE

Drug Info

[28]

Agonist

[+] 2 Agonist drugs

AGN-199981

Drug Info

[3]

xylazine

Drug Info

[34]

Antagonist

[+] 5 Antagonist drugs

imiloxan

Drug Info

[30]

spiroxatrine

Drug Info

[33]

[3H]MK-912

Drug Info

[33]

[3H]rauwolscine

Drug Info

[35]

[3H]RX821002

Drug Info

[36], [37]

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(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

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 2 KEGG Pathways

cGMP-PKG signaling pathway

Neuroactive ligand-receptor interaction

Panther Pathway

[+] 2 Panther Pathways

Alpha adrenergic receptor signaling pathway

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

Reactome

[+] 4 Reactome Pathways

Adrenoceptors

Adrenaline signalling through Alpha-2 adrenergic receptor

G alpha (i) signalling events

G alpha (z) signalling events

WikiPathways

[+] 5 WikiPathways

Monoamine GPCRs

GPCRs, Class A Rhodopsin-like

Platelet Aggregation (Plug Formation)

GPCR ligand binding

GPCR downstream signaling

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. J Med Chem. 1996 Mar 15;39(6):1193-5.

REF 2

The role of I(1)-imidazoline and alpha(2)-adrenergic receptors in the modulation of glucose metabolism in the spontaneously hypertensive obese rat ... J Pharmacol Exp Ther. 2003 Aug;306(2):646-57.

REF 3

Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.

REF 4

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 5

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: 501).

REF 6

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 7

REF 8

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006771)

REF 9

A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic recep... J Med Chem. 1994 Jul 22;37(15):2328-33.

REF 10

Alpha- and beta-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. J Med Chem. 1995 Sep 1;38(18):3415-44.

REF 11

A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. J Med Chem. 1994 Apr 15;37(8):1060-2.

REF 12

Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking... J Med Chem. 2005 Mar 24;48(6):2054-71.

REF 13

Design and synthesis of novel dihydropyridine alpha-1a antagonists. Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.

REF 14

alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs. J Med Chem. 1982 Dec;25(12):1389-401.

REF 15

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

REF 16

3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines display remarkable potency and selectivity as inhibitors of phenylethanolamine N-methyltransferas... J Med Chem. 1999 Jun 3;42(11):1982-90.

REF 17

Synthesis and structure-activity relationships of N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine) and related analogs as potential therapeu... J Med Chem. 1996 Jan 19;39(2):570-81.

REF 18

Effect of ring size or an additional heteroatom on the potency and selectivity of bicyclic benzylamine-type inhibitors of phenylethanolamine N-meth... J Med Chem. 1996 Aug 30;39(18):3539-46.

REF 19

Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines. J Med Chem. 1984 Sep;27(9):1182-5.

REF 20

N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic and dopaminergic activity studies. J Med Chem. 1998 Oct 8;41(21):4165-70.

REF 21

Examination of the role of the acidic hydrogen in imparting selectivity of 7-(aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) toward inh... J Med Chem. 1997 Dec 5;40(25):3997-4005.

REF 22

Pyrazino[1,2-a]indoles as novel high-affinity and selective imidazoline I(2) receptor ligands. Bioorg Med Chem Lett. 2004 Feb 23;14(4):1003-5.

REF 23

Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phen... J Med Chem. 2006 Sep 7;49(18):5424-33.

REF 24

Probes for imidazoline binding sites: synthesis and evaluation of a selective, irreversible I2 ligand. Bioorg Med Chem Lett. 2000 Mar 20;10(6):605-7.

REF 25

3-hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline inhibitors of phenylethanolamine N-methyltransferase that display re... J Med Chem. 2005 Jan 13;48(1):134-40.

REF 26

Medetomidine analogs as alpha 2-adrenergic ligands. 3. Synthesis and biological evaluation of a new series of medetomidine analogs and their potent... J Med Chem. 1997 Sep 12;40(19):3014-24.

REF 27

alpha(2) Adrenoceptor agonists as potential analgesic agents. 2. Discovery of 4-(4-Imidazo)-1,3-dimethyl-6,7-dihydrothianaphthene [corrected] as a ... J Med Chem. 2000 Mar 9;43(5):765-8.

REF 28

Binding of an imidazopyridoindole at imidazoline I2 receptors. Bioorg Med Chem Lett. 2004 Jan 19;14(2):527-9.

REF 29

Structure-activity relationship of quinoline derivatives as potent and selective alpha(2C)-adrenoceptor antagonists. J Med Chem. 2006 Oct 19;49(21):6351-63.

REF 30

Assessment of imiloxan as a selective alpha 2B-adrenoceptor antagonist. Br J Pharmacol. 1990 Mar;99(3):560-4.

REF 31

4-Amino-6-chloro-2-piperazinopyrimidines with selective affinity for alpha 2-adrenoceptors. J Med Chem. 1986 Aug;29(8):1394-8.

REF 32

Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-a... Bioorg Med Chem. 2007 Jun 1;15(11):3649-60.

REF 33

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 34

Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding. Biochem Pharmacol. 1998 Apr 1;55(7):1035-43.

REF 35

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 36

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 37

Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists. J Med Chem. 1986 Oct;29(10):2000-3.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Yuzong CHEN

Prof. Feng ZHU