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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:26
Primary Accession Number DB00598
Secondary Accession Number
  • APRD01062
Name Labetalol
Drug Type
  • Approved
  • Small Molecule
Description Blocker of both alpha- and beta-adrenergic receptors that is used as an antihypertensive. [PubChem]
Synonyms
  1. Labetalol HCL
  2. Labetalol hydrochloride
  3. Labetalolum [INN-Latin]
  4. Labetolol
Brand Names
  1. Albetol
  2. Ibidomide
  3. Normodyne
  4. Presdate
  5. Trandate
Brand Mixtures Not Available
Chemical IUPAC Name 2-hydroxy-5-[1-hydroxy-2-(4-phenylbutan-2-ylamino)ethyl]benzamide
Chemical Formula C19H24N2O3
Chemical Structure Structure
CAS Registry Number 36894-69-6
InChI Identifier InChI=1/C19H24N2O3/c1-13(7-8-14-5-3-2-4-6-14)21-12-18(23)15-9-10-17(22)16(11-15)19(20)24/h2-6,9-11,13,18,21-23H,7-8,12H2,1H3,(H2,20,24)/f/h20H2
InChI Key SGUAFYQXFOLMHL-HPHMPNDVCQ
KEGG Drug Not Available
KEGG Compound C07063 Link Image
PubChem Compound 3869 Link Image
PubChem Substance 9275 Link Image
ChEBI ID Not Available
PharmGKB ID PA450155 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02243539 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/labet.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/nor1301.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Labetalol Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 328.4055
Monoisotopic Molecular Weight 328.1787
State Solid
Melting Point 195-196 oC
Experimental Water Solubility 20 mg/ml (HCl salt) Source: PhysProp
Predicted Water Solubility 5.78e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 2.7 Source: PhysProp
Predicted LogP 1.73 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.75 Calculated using ALOGPS
Experimental Caco2 Permeability -5.03 [ADME Research, USCD]
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES C[C@H](CCC1=CC=CC=C1)NC[C@@H](O)C1=CC(C(N)=O)=C(O)C=C1
Canonical SMILES CC(CCC1=CC=CC=C1)NCC(O)C1=CC(C(N)=O)=C(O)C=C1
Drug Category
  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Sympatholytics
ATC Codes
AHFS Codes
  • 24:24.00
Indication For the management of hypertension.
Pharmacology Labetalol is an alpha-1 and beta adrenergic blocker used to treat high blood pressure. It works by blocking these adrenergic receptors, which slows sinus heart rate, decreases peripheral vascular resistance, and decreases cardiac output.
Mechanism of Action Labetalol has two asymmetric centers and therefore, exists as a molecular complex of two diastereoisomeric pairs. Dilevalol, the R,R' stereoisomer, makes up 25% of racemic labetalol. Labetalol HCl combines both selective, competitive, alpha-1-adrenergic blocking and nonselective, competitive, beta-adrenergic blocking activity in a single substance. In man, the ratios of alpha- to beta- blockade have been estimated to be approximately 1:3 and 1:7 following oral and intravenous (IV) administration, respectively. Beta-2-agonist activity has been demonstrated in animals with minimal beta-1-agonist (ISA) activity detected. In animals, at doses greater than those required for alpha- or beta- adrenergic blockade, a membrane stabilizing effect has been demonstrated.
Absorption Completely absorbed (100%) from the gastrointestinal tract with peak plasma levels occurring 1 to 2 hours after oral administration. The absolute bioavailability of labetalol is increased when administered with food.
Toxicity LD50 = 66 mg/kg (Rat, IV). Side effects or adverse reactions include dizziness when standing up, very low blood pressure, severely slow heartbeat, weakness, diminished sexual function, fatigue
Protein Binding 50%
Biotransformation Primarily hepatic, undergoes significant first pass metabolism
Half Life 6-8 hours
Dosage Forms
Form Route
Liquid Intravenous
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acetohexamide The beta-blocker decreases the symptoms of hypoglycemia
Chlorpropamide The beta-blocker decreases the symptoms of hypoglycemia
Cimetidine Cimetidine increases the effect of the beta-blocker
Clonidine Increased hypertension when clonidine stopped
Dihydroergotamine Ischemia with risk of gangrene
Dihydroergotoxine Ischemia with risk of gangrene
Disopyramide The beta-blocker increases toxicity of disopyramide
Enflurane Monitor arterial pressure closely
Epinephrine Hypertension, then bradycardia
Ergonovine Ischemia with risk of gangrene
Ergotamine Ischemia with risk of gangrene
Fenoterol Antagonism
Formoterol Antagonism
Glibenclamide The beta-blocker decreases the symptoms of hypoglycemia
Gliclazide The beta-blocker decreases the symptoms of hypoglycemia
Glipizide The beta-blocker decreases the symptoms of hypoglycemia
Glisoxepide The beta-blocker decreases the symptoms of hypoglycemia
Glycodiazine The beta-blocker decreases the symptoms of hypoglycemia
Halothane Monitor arterial pressure closely
Ibuprofen Risk of inhibition of renal prostaglandins
Indomethacin Risk of inhibition of renal prostaglandins
Insulin The beta-blocker decreases the symptoms of hypoglycemia
Isoflurane Monitor arterial pressure closely
Isoproterenol Antagonism
Lidocaine The beta-blocker increases the effect and toxicity of lidocaine
Methysergide Ischemia with risk of gangrene
Orciprenaline Antagonism
Pirbuterol Antagonism
Piroxicam Risk of inhibition of renal prostaglandins
Prazosin Risk of hypotension at the beginning of therapy
Procaterol Antagonism
Repaglinide The beta-blocker decreases the symptoms of hypoglycemia
Salbutamol Antagonism
Salmeterol Antagonism
Terbutaline Antagonism
Tolazamide The beta-blocker decreases the symptoms of hypoglycemia
Tolbutamide The beta-blocker decreases the symptoms of hypoglycemia
Verapamil Increased effect of both drugs
Food Interactions
  • Take without regard to meals.
Pathways
Name SMPDB Link KEGG Link
Labetalol Pathway SMP00368 Link Image
General References
  1. Wikipedia Link Image
  2. RxList Link Image
  3. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Beta-1 adrenergic receptor
  2. Alpha-1A adrenergic receptor
  3. Alpha-1B adrenergic receptor
  4. Beta-2 adrenergic receptor
Drug Target 1 [top]
Target 1 ID 193
Target 1 Name Beta-1 adrenergic receptor
Target 1 Synonyms
  1. Beta-1 adrenoceptor
  2. Beta-1 adrenoreceptor
Target 1 Gene Name ADRB1
Target 1 Protein Sequence >Beta-1 adrenergic receptor 
MGAGVLVLGASEPGNLSSAAPLPDGAATAARLLVPASPPASLLPPASESPEPLSQQWTAG
MGLLMALIVLLIVAGNVLVIVAIAKTPRLQTLTNLFIMSLASADLVMGLLVVPFGATIVV
WGRWEYGSFFCELWTSVDVLCVTASIETLCVIALDRYLAITSPFRYQSLLTRARARGLVC
TVWAISALVSFLPILMHWWRAESDEARRCYNDPKCCDFVTNRAYAIASSVVSFYVPLCIM
AFVYLRVFREAQKQVKKIDSCERRFLGGPARPPSPSPSPVPAPAPPPGPPRPAAAAATAP
LANGRAGKRRPSRLVALREQKALKTLGIIMGVFTLCWLPFFLANVVKAFHRELVPDRLFV
FFNWLGYANSAFNPIIYCRSPDFRKAFQRLLCCARRAARRRHATHGDRPRASGCLARPGP
PPSPGAASDDDDDDVVGATPPARLLEPWAGCNGGAAADSDSSLDEPCRPGFASESKV
Target 1 Number of Residues 484
Target 1 Molecular Weight 51323
Target 1 Theoretical pI 9.03
Target 1 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
beta-adrenergic receptor activity
beta1-adrenergic receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in beta1-adrenergic receptor activity
Target 1 Specific Function Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 60-83
  • 97-120
  • 132-155
  • 176-199
  • 222-245
  • 326-349
  • 357-380
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 178200 Link Image
Target 1 UniProtKB/Swiss-Prot ID P08588 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ADRB1_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Cell membrane
  • multi-pass membrane protein. Localized at the plasma membrane. Found in the Golgi upo
Target 1 Gene Sequence >1434 bp 
ATGGGCGCGGGGGTGCTCGTCCTGGGCGCCTCCGAGCCCGGTAACCTGTCGTCGGCCGCA
CCGCTCCCCGACGGCGCGGCCACCGCGGCGCGGCTGCTGGTGCCCGCGTCGCCGCCCGCC
TCGTTGCTGCCTCCCGCCAGCGAAAGCCCCGAGCCGCTGTCTCAGCAGTGGACAGCGGGC
ATGGGTCTGCTGATGGCGCTCATCGTGCTGCTCATCGTGGCGGGCAATGTGCTGGTGATC
GTGGCCATCGCCAAGACGCCGCGGCTGCAGACGCTCACCAACCTCTTCATCATGTCCCTG
GCCAGCGCCGACCTGGTCATGGGGCTGCTGGTGGTGCCGTTCGGGGCCACCATCGTGGTG
TGGGGCCGCTGGGAGTACGGCTCCTTCTTCTGCGAGCTGTGGACCTCAGTGGACGTGCTG
TGCGTGACGGCCAGCATCGAGACCCTGTGTGTCATTGCCCTGGACCGCTACCTCGCCATC
ACCTCGCCCTTCCGCTACCAGAGCCTGCTGACGCGCGCGCGGGCGCGGGGCCTCGTGTGC
ACCGTGTGGGCCATCTCGGCCCTGGTGTCCTTCCTGCCCATCCTCATGCACTGGTGGCGG
GCGGAGAGCGACGAGGCGCGCCGCTGCTACAACGACCCCAAGTGCTGCGACTTCGTCACC
AACCGGGCCTACGCCATCGCCTCGTCCGTAGTCTCCTTCTACGTGCCCCTGTGCATCATG
GCCTTCGTGTACCTGCGGGTGTTCCGCGAGGCCCAGAAGCAGGTGAAGAAGATCGACAGC
TGCGAGCGCCGTTTCCTCGGCGGCCCAGCGCGGCCGCCCTCGCCCTCGCCCTCGCCCGTC
CCCGCGCCCGCGCCGCCGCCCGGACCCCCGCGCCCCGCCGCCGCCGCCGCCACCGCCCCG
CTGGCCAACGGGCGTGCGGGTAAGCGGCGGCCCTCGCGCCTCGTGGCCCTACGCGAGCAG
AAGGCGCTCAAGACGCTGGGCATCATCATGGGCGTCTTCACGCTCTGCTGGCTGCCCTTC
TTCCTGGCCAACGTGGTGAAGGCCTTCCACCGCGAGCTGGTGCCCGACCGCCTCTTCGTC
TTCTTCAACTGGCTGGGCTACGCCAACTCGGCCTTCAACCCCATCATCTACTGCCGCAGC
CCCGACTTCCGCAAGGCCTTCCAGGGACTGCTCTGCTGCGCGCGCAGGGCTGCCCGCCGG
CGCCACGCGACCCACGGAGACCGGCCGCGCGCCTCGGGCTGTCTGGCCCGGCCCGGACCC
CCGCCATCGCCCGGGGCCGCCTCGGACGACGACGACGACGATGTCGTCGGGGCCACGCCG
CCCGCGCGCCTGCTGGAGCCCTGGGCCGGCTGCAACGGCGGGGCGGCGGCGGACAGCGAC
TCGAGCCTGGACGAGCCGTGCCGCCCCGGCTTCGCCTCGGAATCCAAGGTGTAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID ADRB1 Link Image
Target 1 GenAtlas ID ADRB1 Link Image
Target 1 HGNC ID HGNC:285 Link Image
Target 1 Chromosome Location 10
Target 1 Locus 10q24-q26
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Mason DA, Moore JD, Green SA, Liggett SB: A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem. 1999 Apr 30;274(18):12670-4. [PubMed Link Image]
  2. Moore JD, Mason DA, Green SA, Hsu J, Liggett SB: Racial differences in the frequencies of cardiac beta(1)-adrenergic receptor polymorphisms: analysis of c145A>G and c1165G>C. Hum Mutat. 1999 Sep 19;14(3):271. [PubMed Link Image]
  3. Borjesson M, Magnusson Y, Hjalmarson A, Andersson B: A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure. Eur Heart J. 2000 Nov;21(22):1853-8. [PubMed Link Image]
  4. Ranade K, Jorgenson E, Sheu WH, Pei D, Hsiung CA, Chiang FT, Chen YD, Pratt R, Olshen RA, Curb D, Cox DR, Botstein D, Risch N: A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate. Am J Hum Genet. 2002 Apr;70(4):935-42. Epub 2002 Feb 18. [PubMed Link Image]
  5. Frielle T, Collins S, Daniel KW, Caron MG, Lefkowitz RJ, Kobilka BK: Cloning of the cDNA for the human beta 1-adrenergic receptor. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7920-4. [PubMed Link Image]
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  2. Riva E, Mennini T, Latini R: The alpha- and beta-adrenoceptor blocking activities of labetalol and its RR-SR (50:50) stereoisomers. Br J Pharmacol. 1991 Dec;104(4):823-8. [PubMed Link Image]
  3. Monopoli A, Bamonte F, Forlani A, Ongini E, Parravicini L: Effects of the R, R-isomer of labetalol, SCH 19927, in isolated tissues and in spontaneously hypertensive rats during a repeated treatment. Arch Int Pharmacodyn Ther. 1984 Dec;272(2):256-63. [PubMed Link Image]
  4. Sassard J, Zech PY, Pozet N, Cuisinaud G, Vincent M: [Comparative effects of an alpha 1 and beta 1-2 blocker (labetalol) and a beta-1 blocker (atenolol) in the hypertensive patient] J Pharmacol. 1983;14 Suppl 2:121-9. [PubMed Link Image]
  5. Nakagawa Y, Takeda K, Sakurai H, Mitomi A, Imai S: [Antihypertensive effects of labetalol in three types of hypertensive models of rats (author's transl)] Nippon Yakurigaku Zasshi. 1981 Apr;77(4):435-45. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 556
Target 2 Name Alpha-1A adrenergic receptor
Target 2 Synonyms
  1. Alpha 1A- adrenoreceptor
  2. Alpha 1A-adrenoceptor
  3. Alpha adrenergic receptor 1c
  4. Alpha-1C adrenergic receptor
Target 2 Gene Name ADRA1A
Target 2 Protein Sequence >Alpha-1A adrenergic receptor 
MVFLSGNASDSSNCTQPPAPVNISKAILLGVILGGLILFGVLGNILVILSVACHRHLHSV
THYYIVNLAVADLLLTSTVLPFSAIFEVLGYWAFGRVFCNIWAAVDVLCCTASIMGLCII
SIDRYIGVSYPLRYPTIVTQRRGLMALLCVWALSLVISIGPLFGWRQPAPEDETICQINE
EPGYVLFSALGSFYLPLAIILVMYCRVYVVAKRESRGLKSGLKTDKSDSEQVTLRIHRKN
APAGGSGMASAKTKTHFSVRLLKFSREKKAAKTLGIVVGCFVLCWLPFFLVMPIGSFFPD
FKPSETVFKIVFWLGYLNSCINPIIYPCSSQEFKKAFQNVLRIQCLCRKQSSKHALGYTL
HPPSQAVEGQHKDMVRIPVGSRETFYRISKTDGVCEWKFFSSMPRGSARITVSKDQSSCT
TARVRSKSFLQVCCCVGPSTPSLDKNHQVPTIKVHTISLSENGEEV
Target 2 Number of Residues 473
Target 2 Molecular Weight 51487
Target 2 Theoretical pI 9.23
Target 2 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
alpha-adrenergic receptor activity
alpha1-adrenergic receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in alpha1-adrenergic receptor activity
Target 2 Specific Function This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 28-51
  • 65-88
  • 100-122
  • 144-167
  • 182-205
  • 274-297
  • 306-329
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 433201 Link Image
Target 2 UniProtKB/Swiss-Prot ID P35348 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name ADA1A_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >1401 bp 
ATGGTGTTTCTCTCGGGAAATGCTTCCGACAGCTCCAACTGCACCCAACCGCCGGCACCG
GTGAACATTTCCAAGGCCATTCTGCTCGGGGTGATCTTGGGGGGCCTCATTCTTTTCGGG
GTGCTGGGTAACATCCTAGTGATCCTCTCCGTAGCCTGTCACCGACACCTGCACTCAGTC
ACGCACTACTACATCGTCAACCTGGCGGTGGCCGACCTCCTGCTCACCTCCACGGTGCTG
CCCTTCTCCGCCATCTTCGAGGTCCTAGGCTACTGGGCCTTCGGCAGGGTCTTCTGCAAC
ATCTGGGCGGCAGTGGATGTGCTGTGCTGCACCGCGTCCATCATGGGCCTCTGCATCATC
TCCATCGACCGCTACATCGGCGTGAGCTACCCGCTGCGCTACCCAACCATCGTCACCCAG
AGGAGGGGTCTCATGGCTCTGCTCTGCGTCTGGGCACTCTCCCTGGTCATATCCATTGGA
CCCCTGTTCGGCTGGAGGCAGCCGGCCCCCGAGGACGAGACCATCTGCCAGATCAACGAG
GAGCCGGGCTACGTGCTCTTCTCAGCGCTGGGCTCCTTCTACCTGCCTCTGGCCATCATC
CTGGTCATGTACTGCCGCGTCTACGTGGTGGCCAAGAGGGAGAGCCGGGGCCTCAAGTCT
GGCCTCAAGACCGACAAGTCGGACTCGGAGCAAGTGACGCTCCGCATCCATCGGAAAAAC
GCCCCGGCAGGAGGCAGCGGGATGGCCAGCGCCAAGACCAAGACGCACTTCTCAGTGAGG
CTCCTCAAGTTCTCCCGGGAGAAGAAAGCGGCCAAAACGCTGGGCATCGTGGTCGGCTGC
TTCGTCCTCTGCTGGCTGCCTTTTTTCTTAGTCATGCCCATTGGGTCTTTCTTCCCTGAT
TTCAAGCCCTCTGAAACAGTTTTTAAAATAGTATTTTGGCTCGGATATCTAAACAGCTGC
ATCAACCCCATCATATACCCATGCTCCAGCCAAGAGTTCAAAAAGGCCTTTCAGAATGTC
TTGAGAATCCAGTGTCTCCGCAGAAAGCAGTCTTCCAAACATGCCCTGGGCTACACCCTG
CACCCGCCCAGCCAGGCCGTGGAAGGGCAACACAAGGACATGGTGCGCATCCCCGTGGGA
TCAAGAGAGACCTTCTACAGGATCTCCAAGACGGATGGCGTTTGTGAATGGAAATTTTTC
TCTTCCATGCCCCGTGGATCTGCCAGGATTACAGTGTCCAAAGACCAATCCTCCTGTACC
ACAGCCCGGGTGAGAAGTAAAAGCTTTTTGGAGGTCTGCTGCTGTGTAGGGCCCTCAACC
CCCAGCCTTGACAAGAACCATCAAGTTCCAACCATTAAGGTCCACACCATCTCCCTCAGT
GAGAACGGGGAGGAAGTCTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID ADRA1A Link Image
Target 2 GenAtlas ID ADRA1A Link Image
Target 2 HGNC ID HGNC:277 Link Image
Target 2 Chromosome Location 8
Target 2 Locus 8p21-p11.2
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Hirasawa A, Shibata K, Horie K, Takei Y, Obika K, Tanaka T, Muramoto N, Takagaki K, Yano J, Tsujimoto G: Cloning, functional expression and tissue distribution of human alpha 1c-adrenoceptor splice variants. FEBS Lett. 1995 Apr 24;363(3):256-60. [PubMed Link Image]
  2. Schwinn DA, Johnston GI, Page SO, Mosley MJ, Wilson KH, Worman NP, Campbell S, Fidock MD, Furness LM, Parry-Smith DJ, et al.: Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues. J Pharmacol Exp Ther. 1995 Jan;272(1):134-42. [PubMed Link Image]
  3. Weinberg DH, Trivedi P, Tan CP, Mitra S, Perkins-Barrow A, Borkowski D, Strader CD, Bayne M: Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c. Biochem Biophys Res Commun. 1994 Jun 30;201(3):1296-304. [PubMed Link Image]
  4. Forray C, Bard JA, Wetzel JM, Chiu G, Shapiro E, Tang R, Lepor H, Hartig PR, Weinshank RL, Branchek TA, et al.: The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol. 1994 Apr;45(4):703-8. [PubMed Link Image]
  5. Hirasawa A, Horie K, Tanaka T, Takagaki K, Murai M, Yano J, Tsujimoto G: Cloning, functional expression and tissue distribution of human cDNA for the alpha 1C-adrenergic receptor. Biochem Biophys Res Commun. 1993 Sep 15;195(2):902-9. [PubMed Link Image]
  6. Tseng-Crank J, Kost T, Goetz A, Hazum S, Roberson KM, Haizlip J, Godinot N, Robertson CN, Saussy D: The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types. Br J Pharmacol. 1995 Aug;115(8):1475-85. [PubMed Link Image]
  7. Chang DJ, Chang TK, Yamanishi SS, Salazar FH, Kosaka AH, Khare R, Bhakta S, Jasper JR, Shieh IS, Lesnick JD, Ford AP, Daniels DV, Eglen RM, Clarke DE, Bach C, Chan HW: Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms. FEBS Lett. 1998 Jan 30;422(2):279-83. [PubMed Link Image]
Target 2 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 632
Target 3 Name Alpha-1B adrenergic receptor
Target 3 Synonyms
  1. Alpha 1B- adrenoreceptor
  2. Alpha 1B-adrenoceptor
Target 3 Gene Name ADRA1B
Target 3 Protein Sequence >Alpha-1B adrenergic receptor 
MNPDLDTGHNTSAPAHWGELKNANFTGPNQTSSNSTLPQLDITRAISVGLVLGAFILFAI
VGNILVILSVACNRHLRTPTNYFIVNLAMADLLLSFTVLPFSAALEVLGYWVLGRIFCDI
WAAVDVLCCTASILSLCAISIDRYIGVRYSLQYPTLVTRRKAILALLSVWVLSTVISIGP
LLGWKEPAPNDDKECGVTEEPFYALFSSLGSFYIPLAVILVMYCRVYIVAKRTTKNLEAG
VMKEMSNSKELTLRIHSKNFHEDTLSSTKAKGHNPRSSIAVKLFKFSREKKAAKTLGIVV
GMFILCWLPFFIALPLGSLFSTLKPPDAVFKVVFWLGYFNSCLNPIIYPCSSKEFKRAFV
RILGCQCRGRGRRRRRRRRRLGGCAYTYRPWTRGGSLERSQSRKDSLDDSGSCLSGSQRT
LPSASPSPGYLGRGAPPPVELCAFPEWKAPGALLSLPAPEPPGRRGRHDSGPLFTFKLLT
EPESPGTDGGASNGGCEAAADVANGQPGFKSNMPLAPGQF
Target 3 Number of Residues 528
Target 3 Molecular Weight 56837
Target 3 Theoretical pI 9.79
Target 3 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
alpha-adrenergic receptor activity
alpha1-adrenergic receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 3 General Function Involved in alpha1-adrenergic receptor activity
Target 3 Specific Function This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 46-70
  • 84-105
  • 116-141
  • 162-182
  • 202-224
  • 296-319
  • 327-340
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein Not Available
Target 3 UniProtKB/Swiss-Prot ID P35368 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name ADA1B_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 3 Gene Sequence Not Available
Target 3 GenBank Gene ID
Target 3 GeneCard ID ADRA1B Link Image
Target 3 GenAtlas ID ADRA1B Link Image
Target 3 HGNC ID HGNC:278 Link Image
Target 3 Chromosome Location 5
Target 3 Locus 5q23-q32
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Ramarao CS, Denker JM, Perez DM, Gaivin RJ, Riek RP, Graham RM: Genomic organization and expression of the human alpha 1B-adrenergic receptor. J Biol Chem. 1992 Oct 25;267(30):21936-45. [PubMed Link Image]
  2. Schwinn DA, Johnston GI, Page SO, Mosley MJ, Wilson KH, Worman NP, Campbell S, Fidock MD, Furness LM, Parry-Smith DJ, et al.: Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues. J Pharmacol Exp Ther. 1995 Jan;272(1):134-42. [PubMed Link Image]
  3. Forray C, Bard JA, Wetzel JM, Chiu G, Shapiro E, Tang R, Lepor H, Hartig PR, Weinshank RL, Branchek TA, et al.: The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol. 1994 Apr;45(4):703-8. [PubMed Link Image]
Target 3 Drug References
  1. Nakamura T, Maruyama K, Ohnuki T, Hattori K, Watanabe K, Nagatomo T: Tamsulosin: assessment of affinityof (3)H-P razosin binding to two alpha-1- adrenoceptor subtypes in the canine aorta. Pharmacology. 1999 Nov;59(5):234-8. [PubMed Link Image]
  2. Bernstein JS, Ebert TJ, Stowe DF, Schmeling WT, Nelson MA, Woods MP: Partial attenuation of hemodynamic responses to rapid sequence induction and intubation with labetalol. J Clin Anesth. 1989;1(6):444-51. [PubMed Link Image]
  3. Lynch JJ, Montgomery DG, Lucchesi BR: Cardiac electrophysiologic actions of SCH 19927 (Dilevalol), the R,R-isomer of labetalol. J Pharmacol Exp Ther. 1986 Dec;239(3):719-23. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 766
Target 4 Name Beta-2 adrenergic receptor
Target 4 Synonyms
  1. Beta-2 adrenoceptor
  2. Beta-2 adrenoreceptor
Target 4 Gene Name ADRB2
Target 4 Protein Sequence >Beta-2 adrenergic receptor 
MGQPGNGSAFLLAPNRSHAPDHDVTQQRDEVWVVGMGIVMSLIVLAIVFGNVLVITAIAK
FERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVTAS
IETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQE
AINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRF
HVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQD
NLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNT
GEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL
Target 4 Number of Residues 419
Target 4 Molecular Weight 46557
Target 4 Theoretical pI 7.44
Target 4 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
beta-adrenergic receptor activity
beta2-adrenergic receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 4 General Function Involved in beta2-adrenergic receptor activity
Target 4 Specific Function Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • 35-58
  • 72-95
  • 107-129
  • 151-174
  • 197-220
  • 275-298
  • 306-329
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 29371 Link Image
Target 4 UniProtKB/Swiss-Prot ID P07550 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name ADRB2_HUMAN Link Image
Target 4 PDB ID Not Available
Target 4 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 4 Gene Sequence >1242 bp 
ATGGGGCAACCCGGGAACGGCAGCGCCTTCTTGCTGGCACCCAATAGAAGCCATGCGCCG
GACCACGACGTCACGCAGCAAAGGGACGAGGTGTGGGTGGTGGGCATGGGCATCGTCATG
TCTCTCATCGTCCTGGCCATCGTGTTTGGCAATGTGCTGGTCATCACAGCCATTGCCAAG
TTCGAGCGTCTGCAGACGGTCACCAACTACTTCATCACTTCACTGGCCTGTGCTGATCTG
GTCATGGGCCTGGCAGTGGTGCCCTTTGGGGCCGCCCATATTCTTATGAAAATGTGGACT
TTTGGCAACTTCTGGTGCGAGTTTTGGACTTCCATTGATGTGCTGTGCGTCACGGCCAGC
ATTGAGACCCTGTGCGTGATCGCAGTGGATCGCTACTTTGCCATTACTTCACCTTTCAAG
TACCAGAGCCTGCTGACCAAGAATAAGGCCCGGGTGATCATTCTGATGGTGTGGATTGTG
TCAGGCCTTACCTCCTTCTTGCCCATTCAGATGCACTGGTACCGGGCCACCCACCAGGAA
GCCATCAACTGCTATGCCAATGAGACCTGCTGTGACTTCTTCACGAACCAAGCCTATGCC
ATTGCCTCTTCCATCGTGTCCTTCTACGTTCCCCTGGTGATCATGGTCTTCGTCTACTCC
AGGGTCTTTCAGGAGGCCAAAAGGCAGCTCCAGAAGATTGACAAATCTGAGGGCCGCTTC
CATGTCCAGAACCTTAGCCAGGTGGAGCAGGATGGGCGGACGGGGCATGGACTCCGCAGA
TCTTCCAAGTTCTGCTTGAAGGAGCACAAAGCCCTCAAGACGTTAGGCATCATCATGGGC
ACTTTCACCCTCTGCTGGCTGCCCTTCTTCATCGTTAACATTGTGCATGTGATCCAGGAT
AACCTCATCCGTAAGGAAGTTTACATCCTCCTAAATTGGATAGGCTATGTCAATTCTGGT
TTCAATCCCCTTATCTACTGCCGGAGCCCAGATTTCAGGATTGCCTTCCAGGAGCTTCTG
TGCCTGCGCAGGTCTTCTTTGAAGGCCTATGGGAATGGCTACTCCAGCAACGGCAACACA
GGGGAGCAGAGTGGATATCACGTGGAACAGGAGAAAGAAAATAAACTGCTGTGTGAAGAC
CTCCCAGGCACGGAAGACTTTGTGGGCCATCAAGGTACTGTGCCTAGCGATAACATTGAT
TCACAAGGGAGGAATTGTAGTACAAATGACTCACTGCTGTAA
Target 4 GenBank Gene ID
Target 4 GeneCard ID ADRB2 Link Image
Target 4 GenAtlas ID ADRB2 Link Image
Target 4 HGNC ID HGNC:286 Link Image
Target 4 Chromosome Location 5
Target 4 Locus 5q31-q32
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M: A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. Nature. 1999 Sep 16;401(6750):286-90. [PubMed Link Image]
  2. Moffett S, Rousseau G, Lagace M, Bouvier M: The palmitoylation state of the beta(2)-adrenergic receptor regulates the synergistic action of cyclic AMP-dependent protein kinase and beta-adrenergic receptor kinase involved in its phosphorylation and desensitization. J Neurochem. 2001 Jan;76(1):269-79. [PubMed Link Image]
  3. O'Dowd BF, Hnatowich M, Caron MG, Lefkowitz RJ, Bouvier M: Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor. J Biol Chem. 1989 May 5;264(13):7564-9. [PubMed Link Image]
  4. Emorine LJ, Marullo S, Delavier-Klutchko C, Kaveri SV, Durieu-Trautmann O, Strosberg AD: Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization. Proc Natl Acad Sci U S A. 1987 Oct;84(20):6995-9. [PubMed Link Image]
  5. Chung FZ, Wang CD, Potter PC, Venter JC, Fraser CM: Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation. J Biol Chem. 1988 Mar 25;263(9):4052-5. [PubMed Link Image]
  6. Kobilka BK, Dixon RA, Frielle T, Dohlman HG, Bolanowski MA, Sigal IS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ: cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor. Proc Natl Acad Sci U S A. 1987 Jan;84(1):46-50. [PubMed Link Image]
  7. Chung FZ, Lentes KU, Gocayne J, Fitzgerald M, Robinson D, Kerlavage AR, Fraser CM, Venter JC: Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors. FEBS Lett. 1987 Jan 26;211(2):200-6. [PubMed Link Image]
  8. Schofield PR, Rhee LM, Peralta EG: Primary structure of the human beta-adrenergic receptor gene. Nucleic Acids Res. 1987 Apr 24;15(8):3636. [PubMed Link Image]
  9. Kobilka BK, Frielle T, Dohlman HG, Bolanowski MA, Dixon RA, Keller P, Caron MG, Lefkowitz RJ: Delineation of the intronless nature of the genes for the human and hamster beta 2-adrenergic receptor and their putative promoter regions. J Biol Chem. 1987 May 25;262(15):7321-7. [PubMed Link Image]
  10. Turki J, Pak J, Green SA, Martin RJ, Liggett SB: Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype. J Clin Invest. 1995 Apr;95(4):1635-41. [PubMed Link Image]
  11. 7915137 Green SA, Turki J, Innis M, Liggett SB: Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry. 1994 Aug 16;33(32):9414-9.
  12. 8383511 Reihsaus E, Innis M, MacIntyre N, Liggett SB: Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol. 1993 Mar;8(3):334-9.
Target 4 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  2. Doggrell SA: The effects of labetalol and dilevalol on isolated cardiovascular preparations of the guinea-pig and rat. J Pharm Pharmacol. 1992 Dec;44(12):1001-6. [PubMed Link Image]
  3. Doggrell SA: Relaxant and beta 2-adrenoceptor blocking activities of labetalol, dilevalol, amosulalol and KF-4317 on the rat isolated aorta. J Pharm Pharmacol. 1988 Nov;40(11):812-5. [PubMed Link Image]
  4. Lunell NO, Fredholm B, Hjemdahl P, Lewander R, Nisell H, Nylund L, Persson B, Sarby B, Wager J: Labetalol, a combined alpha- and beta-blocker, in hypertension of pregnancy. Acta Med Scand Suppl. 1982;665:143-7. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.