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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:05:59
Primary Accession Number DB00692
Secondary Accession Number
  • APRD00615
Name Phentolamine
Drug Type
  • Approved
  • Small Molecule
Description A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of raynaud disease and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. [PubChem]
Synonyms Not Available
Brand Names
  1. Phenotolamine
  2. Phentalamine
  3. Phentolamine Mesilate
  4. Phentolamine Mesylate
  5. Phentolamine Mesylate [USAN]
  6. Phentolamine Methanesulfonate
  7. Phentolamine Methanesulphonate
  8. Phentolamine, Methyl Sulfonate
  9. Regitin
  10. Regitin Methanesulphonate
  11. Regitine
  12. Regitine Mesylate
  13. Regitine Methanesulfonate
  14. Regitipe
  15. Rogitine
Brand Mixtures Not Available
Chemical IUPAC Name 3-[4,5-dihydro-1H-imidazol-2-ylmethyl-(4-methylphenyl)amino]phenol
Chemical Formula C17H19N3O
Chemical Structure Structure
CAS Registry Number 50-60-2
InChI Identifier InChI=1/C17H19N3O/c1-13-5-7-14(8-6-13)20(12-17-18-9-10-19-17)15-3-2-4-16(21)11-15/h2-8,11,21H,9-10,12H2,1H3,(H,18,19)/f/h18H
InChI Key MRBDMNSDAVCSSF-GPQMBLKYCH
KEGG Drug Not Available
KEGG Compound Not Available
PubChem Compound 5775 Link Image
PubChem Substance 148562 Link Image
ChEBI ID Not Available
PharmGKB ID Not Available
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02243737 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/phentol.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Phentolamine Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 281.3523
Monoisotopic Molecular Weight 281.1528
State Solid
Melting Point 174.5 oC
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 2.72e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.3 Source: PhysProp
Predicted LogP 2.91 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.02 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
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 CC1=CC=C(C=C1)N(CC1=NCCN1)C1=CC(O)=CC=C1
Canonical SMILES CC1=CC=C(C=C1)N(CC1=NCCN1)C1=CC(O)=CC=C1
Drug Category
  • Adrenergic alpha-Antagonists
  • Antihypertensive Agents
  • Sympatholytics
ATC Codes
AHFS Codes
  • 12:16.00
Indication For the prevention or treatment of dermal necrosis and sloughing following intravenous administration or extravasation of norepinephrine. Also for the prevention or control of hypertensive episodes that may occur in a patient with pheochromocytoma as a result of stress or manipulation during preoperative preparation and surgical excision.
Pharmacology Phentolamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phentolamine is a long-acting, adrenergic, alpha-receptor blocking agent which can produce and maintain "chemical sympathectomy" by oral administration. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. Phentolamine works by blocking alpha receptors in certain parts of the body. Alpha receptors are present in the muscle that lines the walls of blood vessels. When the receptors are blocked by Phentolamine, the muscle relaxes and the blood vessels widen. This widening of the blood vessels results in a lowering of blood pressure.
Mechanism of Action Phentolamine produces its therapeutic actions by blocking alpha receptors, leading to a muscle relaxation and a widening of the blood vessels. This widening of the blood vessels results in a lowering of blood pressure.
Absorption Not Available
Toxicity Not Available
Protein Binding Not Available
Biotransformation Not Available
Half Life 19 minutes
Dosage Forms
Form Route
Solution Intravenous
Tablet, extended release Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Alpha-2A adrenergic receptor
  2. Calcitonin gene-related peptide 1
  3. cAMP-specific 3',5'-cyclic phosphodiesterase 4A
  4. Glucagon
Drug Target 1 [top]
Target 1 ID 318
Target 1 Name Alpha-2A adrenergic receptor
Target 1 Synonyms
  1. Alpha-2 adrenergic receptor subtype C10
  2. Alpha-2A adrenoceptor
  3. Alpha-2A adrenoreceptor
  4. Alpha-2AAR
Target 1 Gene Name ADRA2A
Target 1 Protein Sequence >Alpha-2A adrenergic receptor 
MGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFT
SRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSS
IVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGG
PQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVA
APPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSD
HAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKAS
RWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSS
LNPVIYTIFNHDFRRAFKKILCRGDRKRIV
Target 1 Number of Residues 457
Target 1 Molecular Weight 48957
Target 1 Theoretical pI 10.20
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
alpha-adrenergic receptor activity
alpha2-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 alpha2-adrenergic receptor activity
Target 1 Specific 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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 34-59
  • 71-96
  • 107-129
  • 150-173
  • 193-217
  • 375-399
  • 407-430
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 178196 Link Image
Target 1 UniProtKB/Swiss-Prot ID P08913 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ADA2A_HUMAN Link Image
Target 1 PDB ID 1HOF Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1353 bp 
ATGGGCTCCCTGCAGCCGGACGCGGGCAACGCGAGCTGGAACGGGACCGAGGCGCCGGGG
GGCGGCGCCCGGGCCACCCCTTACTCCCTGCAGGTGACGCTGACGCTGGTGTGCCTGGCC
GGCCTGCTCATGCTGCTCACCGTGTTCGGCAACGTGCTCGTCATCATCGCCGTGTTCACG
AGCCGCGCGCTCAAGGCGCCCCAAAACCTCTTCCTGGTGTCTCTGGCCTCGGCCGACATC
CTGGTGGCCACGCTCGTCATCCCTTTCTCGCTGGCCAACGAGGTCATGGGCTACTGGTAC
TTCGGCAAGGCTTGGTGCGAGATCTACCTGGCGCTCGACGTGCTCTTCTGCACGTCGTCC
ATCGTGCACCTGTGCGCCATCAGCCTGGACCGCTACTGGTCCATCACACAGGCCATCGAG
TACAACCTGAAGCGCACGCCGCGCCGCATCAAGGCCATCATCATCACCGTGTGGGTCATC
TCGGCCGTCATCTCCTTCCCGCCGCTCATCTCCATCGAGAAGAAGGGCGGCGGCGGCGGC
CCGCAGCCGGCCGAGCCGCGCTGCGAGATCAACGACCAGAAGTGGTACGTCATCTCGTCG
TGCATCGGCTCCTTCTTCGCTCCCTGCCTCATCATGATCCTGGTCTACGTGCGCATCTAC
CAGATCGCCAAGCGTCGCACCCGCGTGCCACCCAGCCGCCGGGGTCCGGACGCCGTCGCC
GCGCCGCCGGGGGGCACCGAGCGCAGGCCCAACGGTCTGGGCCCCGAGCGCAGCGCGGGC
CCGGGGGGCGCAGAGGCCGAACCGCTGCCCACCCAGCTCAACGGCGCCCCTGGCGAGCCC
GCGCCGGCCGGGCCGCGCGACACCGACGCGCTGGACCTGGAGGAGAGCTCGTCTTCCGAC
CACGCCGAGCGGCCTCCAGGGCCCCGCAGACCCGAGCGCGGTCCCCGGGGCAAAGGCAAG
GCCCGAGCGAGCCAGGTGAAGCCGGGCGACAGCCTGCGCGGCGCGGGCCGGGGGCGACGG
GGATCGGGACGCCGGCTGCAGGGCCGGGGGAGGAGCGCGTCGGGGCTGCCAAGGCGTCGC
GCTGGCGCGGGCGGGCAGAACCGCGAGAAGCGCTTCACGTTCGTGCTGGCCGTGGTCATC
GGAGTGTTCGTGGTGTGCTGGTTCCCCTTCTTCTTCACCTACACGCTCACGGCCGTCGGG
TGCTCCGTGCCACGCACGCTCTTCAAATTCTTCTTCTGGTTCGGCTACTGCAACAGCTCG
TTGAACCCGGTCATCTACACCATCTTCAACCACGATTTCCGCCGCGCCTTCAAGAAGATC
CTCTGTCGGGGGGACAGGAAGCGGATCGTGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ADRA2A Link Image
Target 1 GenAtlas ID ADRA2A Link Image
Target 1 HGNC ID HGNC:281 Link Image
Target 1 Chromosome Location 10
Target 1 Locus 10q24-q26
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Chung DA, Zuiderweg ER, Fowler CB, Soyer OS, Mosberg HI, Neubig RR: NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix. Biochemistry. 2002 Mar 19;41(11):3596-604. [PubMed Link Image]
  2. Suryanarayana S, Daunt DA, Von Zastrow M, Kobilka BK: A point mutation in the seventh hydrophobic domain of the alpha 2 adrenergic receptor increases its affinity for a family of beta receptor antagonists. J Biol Chem. 1991 Aug 15;266(23):15488-92. [PubMed Link Image]
  3. Wang CD, Buck MA, Fraser CM: Site-directed mutagenesis of alpha 2A-adrenergic receptors: identification of amino acids involved in ligand binding and receptor activation by agonists. Mol Pharmacol. 1991 Aug;40(2):168-79. [PubMed Link Image]
  4. Chhajlani V, Rangel N, Uhlen S, Wikberg JE: Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR. FEBS Lett. 1991 Mar 25;280(2):241-4. [PubMed Link Image]
  5. Guyer CA, Horstman DA, Wilson AL, Clark JD, Cragoe EJ Jr, Limbird LE: Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs. J Biol Chem. 1990 Oct 5;265(28):17307-17. [PubMed Link Image]
  6. Fraser CM, Arakawa S, McCombie WR, Venter JC: Cloning, sequence analysis, and permanent expression of a human alpha 2-adrenergic receptor in Chinese hamster ovary cells. Evidence for independent pathways of receptor coupling to adenylate cyclase attenuation and activation. J Biol Chem. 1989 Jul 15;264(20):11754-61. [PubMed Link Image]
  7. Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ, Regan JW: Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science. 1987 Oct 30;238(4827):650-6. [PubMed Link Image]
Target 1 Drug References
  1. Molderings GJ, Bonisch H, Bruss M, Likungu J, Gothert M: Species-specific pharmacological properties of human alpha(2A)-adrenoceptors. Hypertension. 2000 Sep;36(3):405-10. [PubMed Link Image]
  2. Trendelenburg AU, Meyer A, Klebroff W, Guimaraes S, Starke K: Crosstalk between presynaptic angiotensin receptors, bradykinin receptors and alpha 2-autoreceptors in sympathetic neurons: a study in alpha 2-adrenoceptor-deficient mice. Br J Pharmacol. 2003 Apr;138(8):1389-402. [PubMed Link Image]
  3. Blandizzi C, Fornai M, Colucci R, Baschiera F, Barbara G, De Giorgio R, De Ponti F, Breschi MC, Del Tacca M: Altered prejunctional modulation of intestinal cholinergic and noradrenergic pathways by alpha2-adrenoceptors in the presence of experimental colitis. Br J Pharmacol. 2003 May;139(2):309-20. [PubMed Link Image]
  4. Polak J, Moro C, Klimcakova E, Hejnova J, Majercik M, Viguerie N, Langin D, Lafontan M, Stich V, Berlan M: Dynamic strength training improves insulin sensitivity and functional balance between adrenergic alpha 2A and beta pathways in subcutaneous adipose tissue of obese subjects. Diabetologia. 2005 Dec;48(12):2631-40. Epub 2005 Nov 5. [PubMed Link Image]
  5. Vonend O, Habbel S, Stegbauer J, Roth J, Hein L, Rump LC: Alpha(2A)-adrenoceptors regulate sympathetic transmitter release in mice kidneys. Br J Pharmacol. 2007 Jan;150(1):121-7. Epub 2006 Nov 20. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 1861
Target 2 Name Calcitonin gene-related peptide 1
Target 2 Synonyms
  1. Alpha-type CGRP
  2. CGRP-I
  3. Calcitonin gene-related peptide 1 precursor
  4. Calcitonin gene-related peptide I
Target 2 Gene Name CALCA
Target 2 Protein Sequence >Calcitonin gene-related peptide 1 precursor 
MGFQKFSPFLALSILVLLQAGSLHAAPFRSALESSPADPATLSEDEARLLLAALVQDYVQ
MKASELEQEQEREGSRIIAQKRACDTATCVTHRLAGLLSRSGGVVKNNFVPTNVGSKAFG
RRRRDLQA
Target 2 Number of Residues 130
Target 2 Molecular Weight 13899
Target 2 Theoretical pI 9.40
Target 2 GO Classification
Function
signal transducer activity
receptor binding
hormone activity
Process
Not Available
Component
extracellular region
Target 2 General Function Involved in hormone activity
Target 2 Specific Function CGRP induces vasodilation. It dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role. It also elevates platelet cAMP
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-25
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 179828 Link Image
Target 2 UniProtKB/Swiss-Prot ID P06881 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name CALCA_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location Not Available
Target 2 Gene Sequence >387 bp 
ATGGGCTTCCAAAAGTTCTCCCCCTTCCTGGCTCTCAGCATCTTGGTCCTGTTGCAGGCA
GGCAGCCTCCATGCAGCACCATTCAGGTCTGCCCTGGAGAGCAGCCCAGCAGACCCGGCC
ACGCTCAGTGAGGACGAAGCGCGCCTCCTGCTGGCTGCACTGGTGCAGGACTATGTGCAG
ATGAAGGCCAGTGAGCTGGAGCAGGAGCAAGAGAGAGAGGGCTCCAGAATCATTGCCCAG
AAGAGAGCCTGTGACACTGCCACCTGTGTGACTCATCGGCTGGCAGGCTTGCTGAGCAGA
TCAGGGGGTGTGGTGAAGAACAACTTTGTGCCCACCAATGTGGGTTCCAAAGCCTTTGGC
AGGCGCCGCAGGGACCTTCAAGCCTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID CALCA Link Image
Target 2 GenAtlas ID CALCA Link Image
Target 2 HGNC ID HGNC:1437 Link Image
Target 2 Chromosome Location 11
Target 2 Locus 11p15.2-p15.1
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Matsuo H, Eto T: Isolation and characterization of peptides which act on rat platelets, from a pheochromocytoma. Biochem Biophys Res Commun. 1992 May 29;185(1):134-41. [PubMed Link Image]
  2. Breeze AL, Harvey TS, Bazzo R, Campbell ID: Solution structure of human calcitonin gene-related peptide by 1H NMR and distance geometry with restrained molecular dynamics. Biochemistry. 1991 Jan 15;30(2):575-82. [PubMed Link Image]
  3. Hubbard JA, Martin SR, Chaplin LC, Bose C, Kelly SM, Price NC: Solution structures of calcitonin-gene-related-peptide analogues of calcitonin-gene-related peptide and amylin. Biochem J. 1991 May 1;275 ( Pt 3):785-8. [PubMed Link Image]
  4. Edbrooke MR, Parker D, McVey JH, Riley JH, Sorenson GD, Pettengill OS, Craig RK: Expression of the human calcitonin/CGRP gene in lung and thyroid carcinoma. EMBO J. 1985 Mar;4(3):715-24. [PubMed Link Image]
  5. Broad PM, Symes AJ, Thakker RV, Craig RK: Structure and methylation of the human calcitonin/alpha-CGRP gene. Nucleic Acids Res. 1989 Sep 12;17(17):6999-7011. [PubMed Link Image]
  6. Craig RK, Riley JH, Edbrooke MR, Broad PM, Foord SM, Al-Kazwini SJ, Holman JJ, Marshall I: Expression and function of the human calcitonin/alpha-CGRP gene in health and disease. Biochem Soc Symp. 1986;52:91-105. [PubMed Link Image]
  7. Petermann JB, Born W, Chang JY, Fischer JA: Identification in the human central nervous system, pituitary, and thyroid of a novel calcitonin gene-related peptide, and partial amino acid sequence in the spinal cord. J Biol Chem. 1987 Jan 15;262(2):542-5. [PubMed Link Image]
  8. Jonas V, Lin CR, Kawashima E, Semon D, Swanson LW, Mermod JJ, Evans RM, Rosenfeld MG: Alternative RNA processing events in human calcitonin/calcitonin gene-related peptide gene expression. Proc Natl Acad Sci U S A. 1985 Apr;82(7):1994-8. [PubMed Link Image]
  9. Nelkin BD, Rosenfeld KI, de Bustros A, Leong SS, Roos BA, Baylin SB: Structure and expression of a gene encoding human calcitonin and calcitonin gene related peptide. Biochem Biophys Res Commun. 1984 Sep 17;123(2):648-55. [PubMed Link Image]
  10. Morris HR, Panico M, Etienne T, Tippins J, Girgis SI, MacIntyre I: Isolation and characterization of human calcitonin gene-related peptide. Nature. 1984 Apr 19-25;308(5961):746-8. [PubMed Link Image]
  11. 6610687 Steenbergh PH, Hoppener JW, Zandberg J, Van de Ven WJ, Jansz HS, Lips CJ: Calcitonin gene related peptide coding sequence is conserved in the human genome and is expressed in medullary thyroid carcinoma. J Clin Endocrinol Metab. 1984 Aug;59(2):358-60.
Target 2 Drug References
  1. Rasmussen TN, Schmidt P, Poulsen SS, Holst JJ: Localisation and neural control of the release of calcitonin gene-related peptide (CGRP) from the isolated perfused porcine ileum. Regul Pept. 2001 Apr 20;98(3):137-43. [PubMed Link Image]
  2. Slehria S, Rajvanshi P, Ito Y, Sokhi RP, Bhargava KK, Palestro CJ, McCuskey RS, Gupta S: Hepatic sinusoidal vasodilators improve transplanted cell engraftment and ameliorate microcirculatory perturbations in the liver. Hepatology. 2002 Jun;35(6):1320-8. [PubMed Link Image]
  3. Maeda Y, Yamada K, Hasegawa T, Nabeshima T: Neuronal mechanism of the inhibitory effect of calcitonin on N-methyl-D-aspartate-induced aversive behavior. Eur J Pharmacol. 1995 Mar 6;275(2):163-70. [PubMed Link Image]
  4. Zink-Lorenz A, Komitowska J, Raue F: Norepinephrine induced calcitonin secretion in rat medullary thyroid carcinoma 6-23 cells: interaction between intracellular calcium and cAMP. Exp Clin Endocrinol Diabetes. 1996;104(1):43-9. [PubMed Link Image]
  5. Li Y, Jiang YC, Owyang C: Central CGRP inhibits pancreatic enzyme secretion by modulation of vagal parasympathetic outflow. Am J Physiol. 1998 Nov;275(5 Pt 1):G957-63. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 1971
Target 3 Name cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Target 3 Synonyms
  1. DPDE2
  2. EC 3.1.4.17
  3. PDE46
Target 3 Gene Name PDE4A
Target 3 Protein Sequence >cAMP-specific 3',5'-cyclic phosphodiesterase 4A 
MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQ
PHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGR
SPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTP
FAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDW
CLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISTTFLDKQNEVEI
PSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTD
QEELLAQELENLNKWGLNIFCVSDYAGGRSLTCIMYMIFQERDLLKKFRIPVDTMVTYML
TLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGV
SNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEDNCDIFQNLSKRQRQSLRKMVIDM
VLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLE
LYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADL
VHPDAQEILDTLEDNRDWYYSAIRQSPSPPPEEESRGPGHPPLPDKFQFELTLEEEEEEE
ISMAQIPCTAQEALTAQGLSGVEEALDATIAWEASPAQESLEVMAQEASLEAELEAVYLT
QQAQSTGSAPVAPDEFSSREEFVVAVSHSSPSALALQSPLLPAWRTLSVSEHAPGLPGLP
STAAEVEAQREHQAAKRACSACAGTFGEDTSALPAPGGGGSGGDPT
Target 3 Number of Residues 900
Target 3 Molecular Weight 98144
Target 3 Theoretical pI 4.87
Target 3 GO Classification
Function
hydrolase activity
hydrolase activity, acting on ester bonds
phosphoric ester hydrolase activity
phosphoric diester hydrolase activity
cyclic-nucleotide phosphodiesterase activity
3',5'-cyclic-nucleotide phosphodiesterase activity
catalytic activity
Process
cellular process
cell communication
signal transduction
Component
Not Available
Target 3 General Function Involved in cAMP phosphodiesterase activity
Target 3 Specific Function Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate
Target 3 Pathways
Name SMPDB Link KEGG Link
Purine metabolism SMP00050 Link Image map00230 Link Image
Target 3 Reactions
  • nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 5'-phosphate
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 347120 Link Image
Target 3 UniProtKB/Swiss-Prot ID P27815 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name PDE4A_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Isoform 4:Membrane
  • peripheral membrane protein. Note=Isoform 4 has propensity for association with
Target 3 Gene Sequence >2661 bp 
ATGGAACCCCCGACCGTCCCCTCGGAAAGGAGCCTGTCTCTGTCACTGCCCGGGCCCCGG
GAGGGCCAGGCCACCCTGAAGCCTCCCCCGCAGCACCTGTGGCGGCAGCCTCGGACCCCC
ATCCGTATCCAGCAGCGCGGCTACTCCGACAGCGCGGAGCGCGCCGAGCGGGAGCGGCAG
CCGCACCGGCCCATAGAGCGCGCCGATGCCATGGACACCAGCGACCGGCCCGGCCTGCGC
ACGACCCGCATGTCCTGGCCCTCGTCCTTCCATGGCACTGGCACCGGCAGCGGCGGCGCG
GGCGGAGGCAGCAGCAGGCGCTTCGAGGCAGAGAATGGGCCGACACCATCTCCTGGCCGC
AGCCCCCTGGACTCGCAGGCGAGCCCAGGACTCGTGCTGCACGCCGGGGCGGCCACCAGC
CAGCGCCGGGAGTCCTTCCTGTACCGCTCAGACAGCGACTATGACATGTCACCCAAGACC
ATGTCCCGGAACTCATCGGTCACCAGCGAGGCGCACGCTGAAGACCTCATCGTAACACCA
TTTGCTCAGGTGCTGGCCAGCCTCCGGAGCGTCCGTAGCAACTTCTCACTCCTGACCAAT
GTGCCCGTTCCCAGTAACAAGCGGTCCCCGCTGGGCGGCCCCACCCCTGTCTGCAAGGCC
ACGCTGTCAGAAGAAACGTGTCAGCAGTTGGCCCGGGAGACTCTGGAGGAGCTGGACTGG
TGTCTGGAGCAGCTGGAGACCATGCAGACCTATCGCTCTGTCAGCGAGATGGCCTCGCAC
AAGTTCAAAAGGATGTTGAACCGTGAGCTCACACACCTGTCAGAAATGAGCAGGTCCGGA
AACCAGGTCTCAGAGTACATTTCCACAACATTCCTGGACAAACAGAATGAAGTGGAGATC
CCATCACCCACGATGAAGGAACGAGAAAAACAGCAAGCGCCGCGACCAAGACCCTCCCAG
CCGCCCCCGCCCCCTGTACCACACTTACAGCCCATGTCCCAAATCACAGGGTTGAAAAAG
TTGATGCATAGTAACAGCCTGAACAACTCTAACATTCCCCGATTTGGGGTGAAGACCGAT
CAAGAAGAGCTCCTGGCCCAAGAACTGGAGAACCTGAACAAGTGGGGCCTGAACATCTTT
TGCGTGTCGGATTACGCTGGAGGCCGCTCACTCACCTGCATCATGTACATGATATTCCAG
GAGCGGGACCTGCTGAAGAAATTCCGCATCCCGGTGGACACGATGGTGACATACATGCTG
ACGCTGGAGGATCACTACCACGCTGACGTGGCCTACCATAACAGCCTGCACGCAGCTGAC
GTGCTGCAGTCCACCCACGTACTGCTGGCCACGCCTGCACTAGATGCAGTGTTCACGGAC
CTGGAGATTCTCGCCGCCCTCTTCGCGGCTGCCATCCACGATGTGGATCACCCTGGGGTC
TCCAACCAGTTCCTCATCAACACCAATTCGGAGCTGGCGCTCATGTACAACGATGAGTCG
GTGCTCGAGAATCACCACCTGGCCGTGGGCTTCAAGCTGCTGCAGGAGGACAACTGCGAC
ATCTTCCAGAACCTCAGCAAGCGCCAGCGGCAGAGCCTACGCAAGATGGTCATCGACATG
GTGCTGGCCACGGACATGTCCAAGCACATGACCCTCCTGGCTGACCTGAAGACCATGGTG
GAGACCAAGAAAGTGACCAGCTCAGGGGTCCTCCTGCTAGATAACTACTCCGACCGCATC
CAGGTCCTCCGGAACATGGTGCACTGTGCCGACCTCAGCAACCCCACCAAGCCGCTGGAG
CTGTACCGCCAGTGGACAGACCGCATCATGGCCGAGTTCTTCCAGCAGGGTGACCGAGAG
CGCGAGCGTGGCATGGAAATCAGCCCCATGTGTGACAAGCACACTGCCTCCGTGGAGAAG
TCTCAGGTGGGTTTTATTGACTACATTGTGCACCCATTGTGGGAGACCTGGGCGGACCTT
GTCCACCCAGATGCCCAGGAGATCTTGGACACTTTGGAGGACAACCGGGACTGGTACTAC
AGCGCCATCCGGCAGAGCCCATCTCCGCCACCCGAGGAGGAGTCAAGGGGGCCAGGCCAC
CCACCCCTGCCTGACAAGTTCCAGTTTGAGCTGACGCTGGAGGAGGAAGAGGAGGAAGAA
ATATCAATGGCCCAGATACCGTGCACAGCCCAAGAGGCATTGACTGCGCAGGGATTGTCA
GGAGTCGAGGAAGCTCTGGATGCAACCATAGCCTGGGAGGCATCCCCGGCCCAGGAGTCG
TTGGAAGTTATGGCACAGGAAGCATCCCTGGAGGCCGAGCTGGAGGCAGTGTATTTGACA
CAGCAGGCACAGTCCACAGGCAGTGCACCTGTGGCTCCGGATGAGTTCTCGTCCCGGGAG
GAATTCGTGGTTGCTGTAAGCCACAGCAGCCCCTCTGCCCTGGCTCTTCAAAGCCCCCTT
CTCCCTGCTTGGAGGACCCTGTCTGTTTCAGAGCATGCCCCGGGCCTCCCGGGCCTCCCC
TCCACGGCGGCCGAGGTGGAGGCCCAACGAGAGCACCAGGCTGCCAAGAGGGCTTGCAGT
GCCTGCGCAGGGACATTTGGGGAGGACACATCCGCACTCCCAGCTCCTGGTGGCGGGGGG
TCAGGTGGAGACCCTACCTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID PDE4A Link Image
Target 3 GenAtlas ID PDE4A Link Image
Target 3 HGNC ID HGNC:8780 Link Image
Target 3 Chromosome Location 19
Target 3 Locus 19p13.2
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Livi GP, Kmetz P, McHale MM, Cieslinski LB, Sathe GM, Taylor DP, Davis RL, Torphy TJ, Balcarek JM: Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase. Mol Cell Biol. 1990 Jun;10(6):2678-86. [PubMed Link Image]
  2. Horton YM, Sullivan M, Houslay MD: Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19 [corrected] Biochem J. 1995 Jun 1;308 ( Pt 2):683-91. [PubMed Link Image]
  3. Sullivan M, Egerton M, Shakur Y, Marquardsen A, Houslay MD: Molecular cloning and expression, in both COS-1 cells and S. cerevisiae, of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1). Cell Signal. 1994 Sep;6(7):793-812. [PubMed Link Image]
  4. Bolger G, Michaeli T, Martins T, St John T, Steiner B, Rodgers L, Riggs M, Wigler M, Ferguson K: A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs. Mol Cell Biol. 1993 Oct;13(10):6558-71. [PubMed Link Image]
  5. Sullivan M, Rena G, Begg F, Gordon L, Olsen AS, Houslay MD: Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2. Biochem J. 1998 Aug 1;333 ( Pt 3):693-703. [PubMed Link Image]
Target 3 Drug References
  1. Lue T, Goldstein I, Traish A: Comparison of oral and intracavernosal vasoactive agents in penile erection. Int J Impot Res. 2000 Mar;12 Suppl 1:S81-88. [PubMed Link Image]
  2. Lue T, Goldstein I I, Traish A: Comparison of oral and intracavernosal vasoactive agents in penile erection. Int J Impot Res. 2000 Mar;12(S1):S81-S88. [PubMed Link Image]
  3. Rosen RC: Sexual pharmacology in the 21st century. J Gend Specif Med. 2000 Jul-Aug;3(5):45-52. [PubMed Link Image]
  4. Carson CC: Oral and injectable medications for the treatment of erectile dysfunction. Curr Urol Rep. 2000 Dec;1(4):307-12. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 2097
Target 4 Name Glucagon
Target 4 Synonyms
  1. Glucagon precursor
Target 4 Gene Name GCG
Target 4 Protein Sequence >Glucagon precursor [Contains: Glicentin; Glicentin-related polypeptide 
MKSIYFVAGLFVMLVQGSWQRSLQDTEEKSRSFSASQADPLSDPDQMNEDKRHSQGTFTS
DYSKYLDSRRAQDFVQWLMNTKRNRNNIAKRHDEFERHAEGTFTSDVSSYLEGQAAKEFI
AWLVKGRGRRDFPEEVAIVEELGRRHADGSFSDEMNTILDNLAARDFINWLIQTKITDRK
Target 4 Number of Residues 183
Target 4 Molecular Weight 20909
Target 4 Theoretical pI 6.14
Target 4 GO Classification
Function
signal transducer activity
receptor binding
hormone activity
Process
Not Available
Component
extracellular region
Target 4 General Function Involved in hormone activity
Target 4 Specific Function Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • 1-20
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 183270 Link Image
Target 4 UniProtKB/Swiss-Prot ID P01275 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name GLUC_HUMAN Link Image
Target 4 PDB ID 1GCN Link Image
Target 4 PDB File Show
Target 4 3D Structure
Target 4 Cellular Location
  • Secreted protein
Target 4 Gene Sequence >543 bp 
ATGAAAAGCATTTACTTTGTGGCTGGGTTATTTGTAATGCTGGTACAAGGCAGCTGGCAA
CGTTCCCTTCAAGACACAGAGGAGAAATCCAGATCATTCTCAGCTTCCCAGGCAGACCCA
CTCAGTGATCCTGATCAGATGAACGAGGACAAGCGCCATTCACAGGGCACATTCACCAGT
GACTACAGCAAGTATCTGGACTCCAGGCGTGCCCAAGATTTTGTGCAGTGGTTGATGAAT
ACCAAGAGGAACAGGAATAACATTGCCAAACGTCACGATGAATTTGAGAGACATGCTGAA
GGGACCTTTACCAGTGATGTAAGTTCTTATTTGGAAGGCCAAGCTGCCAAGGAATTCATT
GCTTGGCTGGTGAAAGGCCGAGGAAGGCGAGATTTCCCAGAAGAGGTCGCCATTGTTGAA
GAACTTGGCCGCAGACATGCTGATGGTTCTTTCTCTGATGAGATGAACACCATTCTTGAT
AATCTTGCCGCCAGGGACTTTATAAACTGGTTGATTCAGACCAAAATCACTGACAGGAAA
TAA
Target 4 GenBank Gene ID
Target 4 GeneCard ID GCG Link Image
Target 4 GenAtlas ID GCG Link Image
Target 4 HGNC ID HGNC:4191 Link Image
Target 4 Chromosome Location 2
Target 4 Locus 2q36-q37
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Kieffer TJ, Habener JF: The glucagon-like peptides. Endocr Rev. 1999 Dec;20(6):876-913. [PubMed Link Image]
  2. Chang X, Keller D, O'Donoghue SI, Led JJ: NMR studies of the aggregation of glucagon-like peptide-1: formation of a symmetric helical dimer. FEBS Lett. 2002 Mar 27;515(1-3):165-70. [PubMed Link Image]
  3. Drucker DJ: Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol Endocrinol. 2003 Feb;17(2):161-71. [PubMed Link Image]
  4. Jiang G, Zhang BB: Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E671-8. [PubMed Link Image]
  5. Ying J, Ahn JM, Jacobsen NE, Brown MF, Hruby VJ: NMR solution structure of the glucagon antagonist [desHis1, desPhe6, Glu9]glucagon amide in the presence of perdeuterated dodecylphosphocholine micelles. Biochemistry. 2003 Mar 18;42(10):2825-35. [PubMed Link Image]
  6. Bonic A, Mackin RB: Expression, purification, and PC1-mediated processing of human proglucagon, glicentin, and major proglucagon fragment. Protein Expr Purif. 2003 Mar;28(1):15-24. [PubMed Link Image]
  7. Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, Frost GS, Ghatei MA, Bloom SR: Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab. 2003 Oct;88(10):4696-701. [PubMed Link Image]
  8. Tadokoro R, Shimizu T, Hosaka A, Kaneko N, Satoh Y, Yamashiro Y: Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants. Acta Paediatr. 2003 Oct;92(10):1175-9. [PubMed Link Image]
  9. Orskov C, Bersani M, Johnsen AH, Hojrup P, Holst JJ: Complete sequences of glucagon-like peptide-1 from human and pig small intestine. J Biol Chem. 1989 Aug 5;264(22):12826-9. [PubMed Link Image]
  10. Drucker DJ, Asa S: Glucagon gene expression in vertebrate brain. J Biol Chem. 1988 Sep 25;263(27):13475-8. [PubMed Link Image]
  11. 3725587 White JW, Saunders GF: Structure of the human glucagon gene. Nucleic Acids Res. 1986 Jun 25;14(12):4719-30.
  12. 6877358 Bell GI, Sanchez-Pescador R, Laybourn PJ, Najarian RC: Exon duplication and divergence in the human preproglucagon gene. Nature. 1983 Jul 28-Aug 3;304(5924):368-71.
  13. 8482423 Orskov C, Wettergren A, Holst JJ: Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable. Diabetes. 1993 May;42(5):658-61.
  14. 9287128 Rouille Y, Bianchi M, Irminger JC, Halban PA: Role of the prohormone convertase PC2 in the processing of proglucagon to glucagon. FEBS Lett. 1997 Aug 11;413(1):119-23.
  15. 9667960 Sturm NS, Lin Y, Burley SK, Krstenansky JL, Ahn JM, Azizeh BY, Trivedi D, Hruby VJ: Structure-function studies on positions 17, 18, and 21 replacement analogues of glucagon: the importance of charged residues and salt bridges in glucagon biological activity. J Med Chem. 1998 Jul 16;41(15):2693-700.
Target 4 Drug References
  1. Hoy M, Bokvist K, Xiao-Gang W, Hansen J, Juhl K, Berggren PO, Buschard K, Gromada J: Phentolamine inhibits exocytosis of glucagon by Gi2 protein-dependent activation of calcineurin in rat pancreatic alpha -cells. J Biol Chem. 2001 Jan 12;276(2):924-30. [PubMed Link Image]
  2. Shibata C, Naito H, Jin XL, Ueno T, Funayama Y, Fukushima K, Hashimoto A, Matsuno S, Sasaki I: Effect of glucagon, glicentin, glucagon-like peptide-1 and -2 on interdigestive gastroduodenal motility in dogs with a vagally denervated gastric pouch. Scand J Gastroenterol. 2001 Oct;36(10):1049-55. [PubMed Link Image]
  3. Hansen L, Lampert S, Mineo H, Holst JJ: Neural regulation of glucagon-like peptide-1 secretion in pigs. Am J Physiol Endocrinol Metab. 2004 Nov;287(5):E939-47. [PubMed Link Image]
  4. Mourtada M, Smith SA, Morgan NG: Insulin secretagogues with an imidazoline structure inhibit arginine-induced secretion from isolated glucagon secretion from isolated rat islets of Langerhans. Biochem Biophys Res Commun. 1997 Jul 9;236(1):162-6. [PubMed Link Image]
  5. Giralt M, Vergara P: Sympathetic pathways mediate GLP-1 actions in the gastrointestinal tract of the rat. Regul Pept. 1998 Apr 24;74(1):19-25. [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.