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Showing drug card for Disopyramide (DB00280)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:47:35
Primary Accession Number DB00280
Secondary Accession Number
  • APRD00507
Name Disopyramide
Drug Type
  • Approved
  • Small Molecule
Description A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties. [PubChem]
Synonyms
  1. Disopiramida [INN-Spanish]
  2. Disopyramide Free Base
  3. Disopyramide Phosphate
  4. Disopyramidum [INN-Latin]
Brand Names
  1. Dicorantil
  2. Isorythm
  3. Lispine
  4. Norpace
  5. Norpace CR
  6. Ritmodan
  7. Rythmodan
  8. Rythmodan P
  9. Rythmodan-La
  10. Searle 703
  11. Xi-Disopyramide
Brand Mixtures Not Available
Chemical IUPAC Name 4-(di(propan-2-yl)amino)-2-phenyl-2-pyridin-2-ylbutanamide
Chemical Formula C21H29N3O
Chemical Structure Structure
CAS Registry Number 3737-09-5
InChI Identifier InChI=1/C21H29N3O/c1-16(2)24(17(3)4)15-13-21(20(22)25,18-10-6-5-7-11-18)19-12-8-9-14-23-19/h5-12,14,16-17H,13,15H2,1-4H3,(H2,22,25)/f/h22H2
InChI Key UVTNFZQICZKOEM-MRSUPTMICU
KEGG Drug D00303 Link Image
KEGG Compound C06965 Link Image
PubChem Compound 3114 Link Image
PubChem Substance 162448 Link Image
ChEBI ID Not Available
PharmGKB ID PA449373 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02224828 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/disopyr.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Disopyramide Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 339.4745
Monoisotopic Molecular Weight 339.2311
State Solid
Melting Point 94.5-95 oC
Experimental Water Solubility 44.9 mg/L Source: PhysProp
Predicted Water Solubility 4.93e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.5 Source: PhysProp
Predicted LogP 3.21 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.84 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 CC(C)N(CC[C@](C(N)=O)(C1=CC=CC=C1)C1=CC=CC=N1)C(C)C
Canonical SMILES CC(C)N(CCC(C(N)=O)(C1=CC=CC=C1)C1=CC=CC=N1)C(C)C
Drug Category
  • Anti-Arrhythmia Agents
  • Antiarrhythmic Agents
ATC Codes
AHFS Codes
  • 24:04.04.04
Indication For the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias.
Pharmacology Disopyramide is an antiarrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. In man, Disopyramide at therapeutic plasma levels shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs.
Mechanism of Action Disopyramide is a Type 1 antiarrhythmic drug (ie, similar to procainamide and quinidine). It inhibits the fast sodium channels. In animal studies Disopyramide decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors.
Absorption Nearly complete
Toxicity LD50=580 mg/kg in rats
Protein Binding 50%-65%
Biotransformation Hepatic
Half Life 6.7 hours (range 4-10 hours)
Dosage Forms
Form Route
Capsule Oral
Tablet, extended release Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acebutolol The beta-blocker increases toxicity of disopyramide
Atenolol The beta-blocker increases toxicity of disopyramide
Azithromycin The macrolide increases the effect of disopyramide
Betaxolol The beta-blocker increases toxicity of disopyramide
Bevantolol The beta-blocker increases toxicity of disopyramide
Bisoprolol The beta-blocker increases toxicity of disopyramide
Carteolol The beta-blocker increases toxicity of disopyramide
Carvedilol The beta-blocker increases toxicity of disopyramide
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clarithromycin Increased risk of cardiotoxicity and arrhythmias
Donepezil Possible antagonism of action
Erythromycin Increased risk of cardiotoxicity and arrhythmias
Esmolol The beta-blocker increases toxicity of disopyramide
Ethotoin The hydantoin decreases the effect of disopyramide
Fosphenytoin The hydantoin decreases the effect of disopyramide
Galantamine Possible antagonism of action
Gatifloxacin Increased risk of cardiotoxicity and arrhythmias
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Labetalol The beta-blocker increases toxicity of disopyramide
Levofloxacin Increased risk of cardiotoxicity and arrhythmias
Mephenytoin The hydantoin decreases the effect of disopyramide
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Metoprolol The beta-blocker increases toxicity of disopyramide
Moxifloxacin Increased risk of cardiotoxicity and arrhythmias
Nadolol The beta-blocker increases toxicity of disopyramide
Oxprenolol The beta-blocker increases toxicity of disopyramide
Penbutolol The beta-blocker increases toxicity of disopyramide
Phenobarbital Phenobarbital decreases levels of disopyramide
Phenytoin The hydantoin decreases the effect of disopyramide
Pindolol The beta-blocker increases toxicity of disopyramide
Practolol The beta-blocker increases toxicity of disopyramide
Propranolol The beta-blocker increases toxicity of disopyramide
Quinupristin This combination presents an increased risk of toxicity
Ranolazine Possible additive effect on QT prolongation
Rifampin Rifampin decreases the effect of disopyramide
Rivastigmine Possible antagonism of action
Sotalol The beta-blocker increases toxicity of disopyramide
Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
Telithromycin Increased risk of cardiotoxicity and arrhythmias
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Timolol The beta-blocker increases toxicity of disopyramide
Ziprasidone Increased risk of cardiotoxicity and arrhythmias
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.
Pathways
Name SMPDB Link KEGG Link
Disopyramide Pathway SMP00325 Link Image
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. Sodium channel protein type 5 subunit alpha
  2. Alpha-1-acid glycoprotein 1
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Drug Target 1 [top]
Target 1 ID 220
Target 1 Name Sodium channel protein type 5 subunit alpha
Target 1 Synonyms
  1. HH1
  2. Sodium channel protein type V subunit alpha
  3. Sodium channel protein, cardiac muscle alpha-subunit
  4. Voltage-gated sodium channel subunit alpha Nav1.5
Target 1 Gene Name SCN5A
Target 1 Protein Sequence >Sodium channel protein type 5 subunit alpha 
MANFLLPRGTSSFRRFTRESLAAIEKRMAEKQARGSTTLQESREGLPEEEAPRPQLDLQA
SKKLPDLYGNPPQELIGEPLEDLDPFYSTQKTFIVLNKGKTIFRFSATNALYVLSPFHPV
RRAAVKILVHSLFNMLIMCTILTNCVFMAQHDPPPWTKYVEYTFTAIYTFESLVKILARA
FCLHAFTFLRDPWNWLDFSVIIMAYTTEFVDLGNVSALRTFRVLRALKTISVISGLKTIV
GALIQSVKKLADVMVLTVFCLSVFALIGLQLFMGNLRHKCVRNFTALNGTNGSVEADGLV
WESLDLYLSDPENYLLKNGTSDVLLCGNSSDAGTCPEGYRCLKAGENPDHGYTSFDSFAW
AFLALFRLMTQDCWERLYQQTLRSAGKIYMIFFMLVIFLGSFYLVNLILAVVAMAYEEQN
QATIAETEEKEKRFQEAMEMLKKEHEALTIRGVDTVSRSSLEMSPLAPVNSHERRSKRRK
RMSSGTEECGEDRLPKSDSEDGPRAMNHLSLTRGLSRTSMKPRSSRGSIFTFRRRDLGSE
ADFADDENSTARESESHHTSLLVPWPLRRTSAQGQPSPGTSAPGHALHGKKNSTVDCNGV
VSLLGAGDPEATSPGSHLLRPVMLEHPPDTTTPSEEPGGPQMLTSQAPCVDGFEEPGARQ
RALSAVSVLTSALEELEESRHKCPPCWNRLAQRYLIWECCPLWMSIKQGVKLVVMDPFTD
LTITMCIVLNTLFMALEHYNMTSEFEEMLQVGNLVFTGIFTAEMTFKIIALDPYYYFQQG
WNIFDSIIVILSLMELGLSRMSNLSVLRSFRLLRVFKLAKSWPTLNTLIKIIGNSVGALG
NLTLVLAIIVFIFAVVGMQLFGKNYSELRDSDSGLLPRWHMMDFFHAFLIIFRILCGEWI
ETMWDCMEVSGQSLCLLVFLLVMVIGNLVVLNLFLALLLSSFSADNLTAPDEDREMNNLQ
LALARIQRGLRFVKRTTWDFCCGLLRHRPQKPAALAAQGQLPSCIATPYSPPPPETEKVP
PTRKETQFEEGEQPGQGTPGDPEPVCVPIAVAESDTDDQEEDEENSLGTEEESSKQQESQ
PVSGWPRGPPDSRTWSQVSATASSEAEASASQADWRQQWKAEPQAPGCGETPEDSCSEGS
TADMTNTAELLEQIPDLGQDVKDPEDCFTEGCVRRCPCCAVDTTQAPGKVWWRLRKTCYH
IVEHSWFETFIIFMILLSSGALAFEDIYLEERKTIKVLLEYADKMFTYVFVLEMLLKWVA
YGFKKYFTNAWCWLDFLIVDVSLVSLVANTLGFAEMGPIKSLRTLRALRPLRALSRFEGM
RVVVNALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFGRCINQTEGDLPLNYTIVNN
KSQCESLNLTGELYWTKVKVNFDNVGAGYLALLQVATFKGWMDIMYAAVDSRGYEEQPQW
EYNLYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKK
LGSKKPQKPIPRPLNKYQGFIFDIVTKQAFDVTIMFLICLNMVTMMVETDDQSPEKINIL
AKINLLFVAIFTGECIVKLAALRHYYFTNSWNIFDFVVVILSIVGTVLSDIIQKYFFSPT
LFRVIRLARIGRILRLIRGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYSIFGMANFA
YVKWEAGIDDMFNFQTFANSMLCLFQITTSAGWDGLLSPILNTGPPYCDPTLPNSNGSRG
DCGSPAVGILFFTTYIIISFLIVVNMYIAIILENFSVATEESTEPLSEDDFDMFYEIWEK
FDPEATQFIEYSVLSDFADALSEPLRIAKPNQISLINMDLPMVSGDRIHCMDILFAFTKR
VLGESGEMDALKIQMEEKFMAANPSKISYEPITTTLRRKHEEVSAMVIQRAFRRHLLQRS
LKHASFLFRQQAGSGLSEEDAPEREGLIAYVMSENFSRPLGPPSSSSISSTSFPPSYDSV
TRATSDNLQVRGSDYSHSEDLADFPPSPDRDRESIV
Target 1 Number of Residues 2049
Target 1 Molecular Weight 227165
Target 1 Theoretical pI 5.23
Target 1 GO Classification
Function
voltage-gated ion channel activity
voltage-gated sodium channel activity
transporter activity
ion transporter activity
ion channel activity
Process
cation transport
monovalent inorganic cation transport
sodium ion transport
physiological process
cellular physiological process
transport
ion transport
Component
protein complex
voltage-gated sodium channel complex
cell
membrane
Target 1 General Function Involved in ion channel activity
Target 1 Specific Function This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 127-150
  • 159-178
  • 192-210
  • 217-236
  • 253-276
  • 390-415
  • 712-736
  • 748-771
  • 780-799
  • 806-825
  • 842-862
  • 914-939
  • 1201-1224
  • 1238-1263
  • 1270-1291
  • 1296-1317
  • 1337-1359
  • 1444-1470
  • 1524-1547
  • 1559-1582
  • 1589-1612
  • 1623-1644
  • 1660-1682
  • 1748-1772
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 184039 Link Image
Target 1 UniProtKB/Swiss-Prot ID Q14524 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name SCN5A_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >6051 bp 
ATGGCAAACTTCCTATTACCTCGGGGCACCAGCAGCTTCCGCAGGTTCACACGGGAGTCC
CTGGCAGCCATCGAGAAGCGCATGGCGGAGAAGCAAGCCCGCGGCTCAACCACCTTGCAG
GAGAGCCGAGAGGGGCTGCCCGAGGAGGAGGCTCCCCGGCCCCAGCTGGACCTGCAGGCC
TCCAAAAAGCTGCCAGATCTCTATGGCAATCCACCCCAAGAGCTCATCGGAGAGCCCCTG
GAGGACCTGGACCCCTTCTATAGCACCCAAAAGACTTTCATCGTACTGAATAAAGGCAAG
ACCATCTTCCGGTTCAGTGCCACCAACGCCTTGTATGTCCTCAGTCCCTTCCACCCAGTT
CGGAGAGCGGCTGTGAAGATTCTGGTTCACTCGCTCTTCAACATGCTCATCATGTGCACC
ATCCTCACCAACTGCGTGTTCATGGCCCAGCACGACCCTCCACCCTGGACCAAGTATGTC
GAGTACACCTTCACCGCCATTTACACCTTTGAGTCTCTGGTCAAGATTCTGGCTCGAGCT
TTCTGCCTGCACGCGTTCACTTTCCTTCGGGACCCATGGAACTGGCTGGACTTTAGTGTG
ATTATCATGGCATACACAACTGAATTTGTGGACCTGGGCAATGTCTCAGCCTTACGCACC
TTCCGAGTCCTCCGGGCCCTGAAAACTATATCAGTCATTTCAGGGCTGAAGACCATCGTG
GGGGCCCTGATCCAGTCTGTGAAGAAGCTGGCTGATGTGATGGTCCTCACAGTCTTCTGC
CTCAGCGTCTTTGCCCTCATCGGCCTGCAGCTCTTCATGGGCAACCTAAGGCACAAGTGT
GTGCGCAACTTCACAGCGCTCAACGGCACCAACGGCTCCGTGGAGGCCGACGGCTTGGTC
TGGGAATCCCTGGACCTTTACCTCAGTGATCCAGAAAATTACCTGCTCAAGAACGGCACC
TCTGATGTGTTACTGTGTGGGAACAGCTCTGACGCTGGGACATGTCCGGAGGGCTACCGG
TGCCTAAAGGCAGGCGAGAACCCCGACCACGGCTACACCAGCTTCGATTCCTTTGCCTGG
GCCTTTCTTGCACTCTTCCGCCTGATGACGCAGGACTGCTGGGAGCGCCTCTATCAGCAG
ACCCTCAGGTCCGCAGGGAAGATCTACATGATCTTCTTCATGCTTGTCATCTTCCTGGGG
TCCTTCTACCTGGTGAACCTGATCCTGGCCGTGGTCGCAATGGCCTATGAGGAGCAAAAC
CAAGCCACCATCGCTGAGACCGAGGAGAAGGAAAAGCGCTTCCAGGAGGCCATGGAAATG
CTCAAGAAAGAACACGAGGCCCTCACCATCAGGGGTGTGGATACCGTGTCCCGTAGCTCC
TTGGAGATGTCCCCTTTGGCCCCAGTAAACAGCCATGAGAGAAGAAGCAAGAGGAGAAAA
CGGATGTCTTCAGGAACTGAGGAGTGTGGGGAGGACAGGCTCCCCAAGTCTGACTCAGAA
GATGGTCCCAGAGCAATGAATCATCTCAGCCTCACCCGTGGCCTCAGCAGGACTTCTATG
AAGCCACGTTCCAGCCGCGGGAGCATTTTCACCTTTCGCAGGCGAGACCTGGGTTCTGAA
GCAGATTTTGCAGATGATGAAAACAGCACAGCGCGGGAGAGCGAGAGCCACCACACATCA
CTGCTGGTGCCCTGGCCCCTGCGCCGGACCAGTGCCCAGGGACAGCCCAGTCCCGGAACC
TCGGCTCCTGGCCACGCCCTCCATGGCAAAAAGAACAGCACTGTGGACTGCAATGGGGTG
GTCTCATTACTGGGGGCAGGCGACCCAGAGGCCACATCCCCAGGAAGCCACCTCCTCCGC
CCTGTGATGCTAGAGCACCCGCCAGACACGACCACGCCATCGGAGGAGCCAGGCGGCCCC
CAGATGCTGACCTCCCAGGCTCCGTGTGTAGATGGCTTCGAGGAGCCAGGAGCACGGCAG
CGGGCCCTCAGCGCAGTCAGCGTCCTCACAAGCGCACTGGAAGAGTTAGAGGAGTCTCGC
CACAAGTGTCCACCATGCTGGAACCGTCTCGCCCAGCGCTACCTGATCTGGGAGTGCTGC
CCGCTGTGGATGTCCATCAAGCAGGGAGTGAAGTTGGTGGTCATGGACCCGTTTACTGAC
CTCACCATCACTATGTGCATCGTACTCAACACACTCTTCATGGCGCTGGAGCACTACAAC
ATGACAAGTGAATTCGAGGAGATGCTGCAGGTCGGAAACCTGGTCTTCACAGGGATTTTC
ACAGCAGAGATGACCTTCAAGATCATTGCCCTCGACCCCTACTACTACTTCCAACAGGGC
TGGAACATCTTCGACAGCATCATCGTCATCCTTAGCCTCATGGAGCTGGGCCTGTCCCGC
ATGAGCAACTTGTCGGTGCTGCGCTCCTTCCGCCTGCTGCGGGTCTTCAAGCTGGCCAAA
TCATGGCCCACCCTGAACACACTCATCAAGATCATCGGGAACTCAGTGGGGGCACTGGGG
AACCTGACACTGGTGCTAGCCATCATCGTGTTCATCTTTGCTGTGGTGGGCATGCAGCTC
TTTGGCAAGAACTACTCGGAGCTGAGGGACAGCGACTCAGGCCTGCTGCCTCGCTGGCAC
ATGATGGACTTCTTTCATGCCTTCCTAATCATCTTCCGCATCCTCTGTGGAGAGTGGATC
GAGACCATGTGGGACTGCATGGAGGTGTCGGGGCAGTCATTATGCCTGCTGGTCTTCTTG
CTTGTTATGGTCATTGGCAACCTTGTGGTCCTGAATCTCTTCCTGGCCTTGCTGCTCAGC
TCCTTCAGTGCAGACAACCTCACAGCCCCTGATGAGGACAGAGAGATGAACAACCTCCAG
CTGGCCCTGGCCCGCATCCAGAGGGGCCTGCGCTTTGTCAAGCGGACCACCTGGGATTTC
TGCTGTGGTCTCCTGCGGCACCGGCCTCAGAAGCCCGCAGCCCTTGCCGCCCAGGGCCAG
CTGCCCAGCTGCATTGCCACCCCCTACTCCCCGCCACCCCCAGAGACGGAGAAGGTGCCT
CCCACCCGCAAGGAAACACAGTTTGAGGAAGGCGAGCAACCAGGCCAGGGCACCCCCGGG
GATCCAGAGCCCGTGTGTGTGCCCATCGCTGTGGCCGAGTCAGACACAGATGACCAAGAA
GAGGATGAGGAGAACAGCCTGGGCACGGAGGAGGAGTCCAGCAAGCAGCAGGAATCCCAG
CCTGTGTCCGGCTGGCCCAGAGGCCCTCCGGATTCCAGGACCTGGAGCCAGGTGTCAGCG
ACTGCCTCCTCTGAGGCCGAGGCCAGTGCATCTCAGGCCGACTGGCGGCAGCAGTGGAAA
GCGGAACCCCAGGCCCCAGGGTGCGGTGAGACCCCAGAGGACAGTTGCTCCGAGGGCAGC
ACAGCAGACATGACCAACACCGCTGAGCTCCTGGAGCAGATCCCTGACCTCGGCCAGGAT
GTCAAGGACCCAGAGGACTGCTTCACTGAAGGCTGTGTCCGGCGCTGTCCCTGCTGTGCG
GTGGACACCACACAGGCCCCAGGGAAGGTCTGGTGGCGGTTGCGCAAGACCTGCTACCAC
ATCGTGGAGCACAGCTGGTTCGAGACATTCATCATCTTCATGATCCTACTCAGCAGTGGA
GCGCTGGCCTTCGAGGACATCTACCTAGAGGAGCGGAAGACCATCAAGGTTCTGCTTGAG
TATGCCGACAAGATGTTCACATATGTCTTCGTGCTGGAGATGCTGCTCAAGTGGGTGGCC
TACGGCTTCAAGAAGTACTTCACCAATGCCTGGTGCTGGCTCGACTTCCTCATCGTAGAC
GTCTCTCTGGTCAGCCTGGTGGCCAACACCCTGGGCTTTGCCGAGATGGGCCCCATCAAG
TCACTGCGGACGCTGCGTGCACTCCGTCCTCTGAGAGCTCTGTCACGATTTGAGGGCATG
AGGGTGGTGGTCAATGCCCTGGTGGGCGCCATCCCGTCCATCATGAACGTCCTCCTCGTC
TGCCTCATCTTCTGGCTCATCTTCAGCATCATGGGCGTGAACCTCTTTGCGGGGAAGTTT
GGGAGGTGCATCAACCAGACAGAGGGAGACTTGCCTTTGAACTACACCATCGTGAACAAC
AAGAGCCAGTGTGAGTCCTTGAACTTGACCGGAGAATTGTACTGGACCAAGGTGAAAGTC
AACTTTGACAACGTGGGGGCCGGGTACCTGGCCCTTCTGCAGGTGGCAACATTTAAAGGC
TGGATGGACATTATGTATGCAGCTGTGGACTCCAGGGGGTATGAAGAGCAGCCTCAGTGG
GAATACAACCTCTACATGTACATCTATTTTGTCATTTTCATCATCTTTGGGTCTTTCTTC
ACCCTGAACCTCTTTATTGGTGTCATCATTGACAACTTCAACCAACAGAAGAAAAAGTTA
GGGGGCCAGGACATCTTCATGACAGAGGAGCAGAAGAAGTACTACAATGCCATGAAGAAG
CTGGGCTCCAAGAAGCCCCAGAAGCCCATCCCACGGCCCCTGAACAAGTACCAGGGCTTC
ATATTCGACATTGTGACCAAGCAGGCCTTTGACGTCACCATCATGTTTCTGATCTGCTTG
AATATGGTGACCATGATGGTGGAGACAGATGACCAAAGTCCTGAGAAAATCAACATCTTG
GCCAAGATCAACCTGCTCTTTGTGGCCATCTTCACAGGCGAGTGTATTGTCAAGCTGGCT
GCCCTGCGCCACTACTACTTCACCAACAGCTGGAATATCTTCGACTTCGTGGTTGTCATC
CTCTCCATCGTGGGCACTGTGCTCTCGGACATCATCCAGAAGTACTTCTTCTCCCCGACG
CTCTTCCGAGTCATCCGCCTGGCCCGAATAGGCCGCATCCTCAGACTGATCCGAGGGGCC
AAGGGGATCCGCACGCTGCTCTTTGCCCTCATGATGTCCCTGCCTGCCCTCTTCAACATC
GGGCTGCTGCTCTTCCTCGTCATGTTCATCTACTCCATCTTTGGCATGGCCAACTTCGCT
TATGTCAAGTGGGAGGCTGGCATCGACGACATGTTCAACTTCCAGACCTTCGCCAACAGC
ATGCTGTGCCTCTTCCAGATCACCACGTCGGCCGGCTGGGATGGCCTCCTCAGCCCCATC
CTCAACACTGGGCCGCCCTACTGCGACCCCACTCTGCCCAACAGCAATGGCTCTCGGGGG
GACTGCGGGAGCCCAGCCGTGGGCATCCTCTTCTTCACCACCTACATCATCATCTCCTTC
CTCATCGTGGTCAACATGTACATTGCCATCATCCTGGAGAACTTCAGCGTGGCCACGGAG
GAGAGCACCGAGCCCCTGAGTGAGGACGACTTCGATATGTTCTATGAGATCTGGGAGAAA
TTTGACCCAGAGGCCACTCAGTTTATTGAGTATTCGGTCCTGTCTGACTTTGCCGACGCC
CTGTCTGAGCCACTCCGTATCGCCAAGCCCAACCAGATAAGCCTCATCAACATGGACCTG
CCCATGGTGAGTGGGGACCGCATCCATTGCATGGACATTCTCTTTGCCTTCACCAAAAGG
GTCCTGGGGGAGTCTGGGGAGATGGACGCCCTGAAGATCCAGATGGAGGAGAAGTTCATG
GCAGCCAACCCATCCAAGATCTCCTACGAGCCCATCACCACCACACTCCGGCGCAAGCAC
GAAGAGGTGTCGGCCATGGTTATCCAGAGAGCCTTCCGCAGGCACCTGCTGCAACGCTCT
TTGAAGCATGCCTCCTTCCTCTTCCGTCAGCAGGCGGGCAGCGGCCTCTCCGAAGAGGAT
GCCCCTGAGCGAGAGGGCCTCATCGCCTACGTGATGAGTGAGAACTTCTCCCGACCCCTT
GGCCCACCCTCCAGCTCCTCCATCTCCTCCACTTCCTTCCCACCCTCCTATGACAGTGTC
ACTAGAGCCACCAGCGATAACCTCCAGGTGCGGGGGTCTGACTACAGCCACAGTGAAGAT
CTCGCCGACTTCCCCCCTTCTCCGGACAGGGACCGTGAGTCCATCGTGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID SCN5A Link Image
Target 1 GenAtlas ID SCN5A Link Image
Target 1 HGNC ID HGNC:10593 Link Image
Target 1 Chromosome Location 3
Target 1 Locus 3p21
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Wei J, Wang DW, Alings M, Fish F, Wathen M, Roden DM, George AL Jr: Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel. Circulation. 1999 Jun 22;99(24):3165-71. [PubMed Link Image]
  2. Wattanasirichaigoon D, Vesely MR, Duggal P, Levine JC, Blume ED, Wolff GS, Edwards SB, Beggs AH: Sodium channel abnormalities are infrequent in patients with long QT syndrome: identification of two novel SCN5A mutations. Am J Med Genet. 1999 Oct 29;86(5):470-6. [PubMed Link Image]
  3. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT: Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 Sep 5;102(10):1178-85. [PubMed Link Image]
  4. Wehrens XH, Rossenbacker T, Jongbloed RJ, Gewillig M, Heidbuchel H, Doevendans PA, Vos MA, Wellens HJ, Kass RS: A novel mutation L619F in the cardiac Na+ channel SCN5A associated with long-QT syndrome (LQT3): a role for the I-II linker in inactivation gating. Hum Mutat. 2003 May;21(5):552. [PubMed Link Image]
  5. Gellens ME, George AL Jr, Chen LQ, Chahine M, Horn R, Barchi RL, Kallen RG: Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):554-8. [PubMed Link Image]
  6. Bennett PB, Yazawa K, Makita N, George AL Jr: Molecular mechanism for an inherited cardiac arrhythmia. Nature. 1995 Aug 24;376(6542):683-5. [PubMed Link Image]
  7. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT: SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995 Mar 10;80(5):805-11. [PubMed Link Image]
  8. Wang Q, Shen J, Li Z, Timothy K, Vincent GM, Priori SG, Schwartz PJ, Keating MT: Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia. Hum Mol Genet. 1995 Sep;4(9):1603-7. [PubMed Link Image]
  9. Makita N, Shirai N, Nagashima M, Matsuoka R, Yamada Y, Tohse N, Kitabatake A: A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome. FEBS Lett. 1998 Feb 13;423(1):5-9. [PubMed Link Image]
  10. An RH, Wang XL, Kerem B, Benhorin J, Medina A, Goldmit M, Kass RS: Novel LQT-3 mutation affects Na+ channel activity through interactions between alpha- and beta1-subunits. Circ Res. 1998 Jul 27;83(2):141-6. [PubMed Link Image]
Target 1 Drug References
  1. Shimizu W, Antzelevitch C, Suyama K, Kurita T, Taguchi A, Aihara N, Takaki H, Sunagawa K, Kamakura S: Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2000 Dec;11(12):1320-9. [PubMed Link Image]
  2. Fujiki A, Sugao M, Nishida K, Sakabe M, Tsuneda T, Mizumaki K, Inoue H: Repolarization abnormality in idiopathic ventricular fibrillation: assessment using 24-hour QT-RR and QaT-RR relationships. J Cardiovasc Electrophysiol. 2004 Jan;15(1):59-63. [PubMed Link Image]
  3. Sugao M, Fujiki A, Nishida K, Sakabe M, Tsuneda T, Iwamoto J, Mizumaki K, Inoue H: Repolarization dynamics in patients with idiopathic ventricular fibrillation: pharmacological therapy with bepridil and disopyramide. J Cardiovasc Pharmacol. 2005 Jun;45(6):545-9. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 1181
Target 2 Name Alpha-1-acid glycoprotein 1
Target 2 Synonyms
  1. AGP 1
  2. Alpha-1-acid glycoprotein 1 precursor
  3. OMD 1
  4. Orosomucoid-1
Target 2 Gene Name ORM1
Target 2 Protein Sequence >Alpha-1-acid glycoprotein 1 precursor 
MALSWVLTVLSLLPLLEAQIPLCANLVPVPITNATLDQITGKWFYIASAFRNEEYNKSVQ
EIQATFFYFTPNKTEDTIFLREYQTRQDQCIYNTTYLNVQRENGTISRYVGGQEHFAHLL
ILRDTKTYMLAFDVNDEKNWGLSVYADKPETTKEQLGEFYEALDCLRIPKSDVVYTDWKK
DKCEPLEKQHEKERKQEEGES
Target 2 Number of Residues 204
Target 2 Molecular Weight 23512
Target 2 Theoretical pI 4.66
Target 2 GO Classification
Function
transporter activity
binding
Process
physiological process
cellular physiological process
transport
Component
Not Available
Target 2 General Function Involved in immune modulation
Target 2 Specific Function Appears to function in modulating the activity of the immune system during the acute-phase reaction
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-18
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 757907 Link Image
Target 2 UniProtKB/Swiss-Prot ID P02763 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name A1AG1_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Secreted protein
Target 2 Gene Sequence >606 bp 
ATGGCGCTGTCCTGGGTTCTTACAGTCCTGAGCCTCCTACCTCTGCTGGAAGCCCAGATC
CCATTGTGTGCCAACCTAGTACCGGTGCCCATCACCAACGCCACCCTGGACCAGATCACT
GGCAAGTGGTTTTATATCGCATCGGCCTTTCGAAACGAGGAGTACAATAAGTCGGTTCAG
GAGATCCAAGCAACCTTCTTTTACTTCACCCCCAACAAGACAGAGGACACGATCTTTCTC
AGAGAGTACCAGACCCGACAGGACCAGTGCATCTATAACACCACCTACCTGAATGTCCAG
CGGGAAAATGGGACCATCTCCAGATACGTGGGAGGCCAAGAGCATTTCGCTCACTTGCTG
ATCCTCAGGGACACCAAGACCTACATGCTTGCTTTTGACGTGAACGATGAGAAGAACTGG
GGGCTGTCTGTCTATGCTGACAAGCCAGAGACGACCAAGGAGCAACTGGGAGAGTTCTAC
GAAGCTCTCGACTGCTTGCGCATTCCCAAGTCAGATGTCGTGTACACCGATTGGAAAAAG
GATAAGTGTGAGCCACTGGAGAAGCAGCACGAGAAGGAGAGGAAACAGGAGGAGGGGGAA
TCCTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID ORM1 Link Image
Target 2 GenAtlas ID ORM1 Link Image
Target 2 HGNC ID HGNC:8498 Link Image
Target 2 Chromosome Location 9
Target 2 Locus 9q31-q32
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [PubMed Link Image]
  2. Treuheit MJ, Costello CE, Halsall HB: Analysis of the five glycosylation sites of human alpha 1-acid glycoprotein. Biochem J. 1992 Apr 1;283 ( Pt 1):105-12. [PubMed Link Image]
  3. Dente L, Ciliberto G, Cortese R: Structure of the human alpha 1-acid glycoprotein gene: sequence homology with other human acute phase protein genes. Nucleic Acids Res. 1985 Jun 11;13(11):3941-52. [PubMed Link Image]
  4. Dente L, Pizza MG, Metspalu A, Cortese R: Structure and expression of the genes coding for human alpha 1-acid glycoprotein. EMBO J. 1987 Aug;6(8):2289-96. [PubMed Link Image]
  5. Board PG, Jones IM, Bentley AK: Molecular cloning and nucleotide sequence of human alpha 1 acid glycoprotein cDNA. Gene. 1986;44(1):127-31. [PubMed Link Image]
  6. Ikenaka T, Ishiguro M, Emura J, Kaufmann H, Isemura S, Bauer W, Schmid K: Isolation and partial characterization of the cyanogen bromide fragments of 1 -acid glycoprotein and the elucidation of the amino acid sequence of the carboxyl-terminal cyanogen bromide fragment. Biochemistry. 1972 Sep 26;11(20):3817-29. [PubMed Link Image]
  7. Schmid K, Burgi W, Collins JH, Nanno S: The disulfide bonds of alpha1-acid glycoprotein. Biochemistry. 1974 Jun 18;13(13):2694-7. [PubMed Link Image]
  8. Schmid K, Kaufmann H, Isemura S, Bauer F, Emura J, Motoyama T, Ishiguro M, Nanno S: Structure of 1 -acid glycoprotein. The complete amino acid sequence, multiple amino acid substitutions, and homology with the immunoglobulins. Biochemistry. 1973 Jul 3;12(14):2711-24. [PubMed Link Image]
  9. Yuasa I, Umetsu K, Vogt U, Nakamura H, Nanba E, Tamaki N, Irizawa Y: Human orosomucoid polymorphism: molecular basis of the three common ORM1 alleles, ORM1*F1, ORM1*F2, and ORM1*S. Hum Genet. 1997 Mar;99(3):393-8. [PubMed Link Image]
Target 2 Drug References
  1. Chu JS, Kishion S, Nomura A, Miyazaki K: Serum alpha 1-acid glycoprotein, sialic acid, and protein binding of disopyramide in normal subjects and cardiac patients. Zhongguo Yao Li Xue Bao. 1997 Sep;18(5):408-10. [PubMed Link Image]
  2. Hanada K, Ohta T, Hirai M, Arai M, Ogata H: Enantioselective binding of propranolol, disopyramide, and verapamil to human alpha(1)-acid glycoprotein. J Pharm Sci. 2000 Jun;89(6):751-7. [PubMed Link Image]
  3. Nakagawa T, Kishino S, Itoh S, Sugawara M, Miyazaki K: Differential binding of disopyramide and warfarin enantiomers to human alpha(1)-acid glycoprotein variants. Br J Clin Pharmacol. 2003 Dec;56(6):664-9. [PubMed Link Image]
  4. Haughey DB, Steinberg I, Lee MH: Protein binding of disopyramide--displacement by mono-N-dealkyldisopyramide and variation with source of alpha-1-acid glycoprotein. J Pharm Pharmacol. 1985 Apr;37(4):285-8. [PubMed Link Image]
  5. Brunner F, Muller WE: Prazosin binding to human alpha 1-acid glycoprotein (orosomucoid), human serum albumin, and human serum. Further characterization of the 'single drug binding site' of orosomucoid. J Pharm Pharmacol. 1985 May;37(5):305-9. [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.