Drugbank Logo

Showing drug card for Norfloxacin (DB01059)

Legend: drug field target field enzyme field

for drugs
Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:10
Primary Accession Number DB01059
Secondary Accession Number
  • APRD00469
Name Norfloxacin
Drug Type
  • Approved
  • Small Molecule
Description A synthetic fluoroquinolone (fluoroquinolones) with broad-spectrum antibacterial activity against most gram-negative and gram-positive bacteria. Norfloxacin inhibits bacterial DNA gyrase. [PubChem]
Synonyms Not Available
Brand Names
  1. Chibroxin
  2. Noroxin
Brand Mixtures Not Available
Chemical IUPAC Name 1-ethyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid
Chemical Formula C16H18FN3O3
Chemical Structure Structure
CAS Registry Number 70458-96-7
InChI Identifier InChI=1/C16H18FN3O3/c1-2-19-9-11(16(22)23)15(21)10-7-12(17)14(8-13(10)19)20-5-3-18-4-6-20/h7-9,18H,2-6H2,1H3,(H,22,23)/f/h22H
InChI Key OGJPXUAPXNRGGI-QWOVJGMICW
KEGG Drug D00210 Link Image
KEGG Compound C06687 Link Image
PubChem Compound 4539 Link Image
PubChem Substance 8912 Link Image
ChEBI ID Not Available
PharmGKB ID PA450654 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02246596 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/norfloxacin.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/nor1302.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Norfloxacin Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 319.3308
Monoisotopic Molecular Weight 319.1332
State Solid
Melting Point 227-228 oC
Experimental Water Solubility 1.78E+005 mg/L Source: PhysProp
Predicted Water Solubility 1.01e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 2.1 Source: PhysProp
Predicted LogP -0.46 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.50 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 CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(C=C12)N1CCNCC1
Canonical SMILES CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(C=C12)N1CCNCC1
Drug Category
  • Anti-Bacterial Agents
  • Anti-Infectives
  • Enzyme Inhibitors
  • Nucleic Acid Synthesis Inhibitors
  • Quinolones
ATC Codes
AHFS Codes
  • 08:12.18
Indication For the treatment of urinary tract infection
Pharmacology Norfloxacin is a quinolone/fluoroquinolone antibiotic. Norfloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian.
Mechanism of Action The bactericidal action of Norfloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination. Norfloxacin is a broad-spectrum antibiotic that is active against both gram-positive and gram-negative bacterias. The fluorine atom at the 6 position increases potency against gram-negative organisms, and the piperazine moiety at the 7 position is responsible for anti-pseudomonal activity
Absorption Rapid
Toxicity Not Available
Protein Binding 10 and 15% (Serum protein binding)
Biotransformation Via liver and kidney
Half Life 3-4 hours
Dosage Forms
Form Route
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol The quinolone increases the anticoagulant effect
Aluminium Formation of non-absorbable complexes
Aminophylline The quinolone increases the effect of theophylline
Anisindione The quinolone increases the anticoagulant effect
Bismuth Formation of non-absorbable complexes
Caffeine The quinolone increases the effect and toxicity of caffeine
Calcium Formation of non-absorbable complexes
Clozapine Ciprofloxacin may increase clozapine serum levels
Cyclosporine The quinolone increases the effect and toxicity of cyclosporine
Dicumarol The quinolone increases the anticoagulant effect
Dyphylline The quinolone increases the effect of theophylline
Foscarnet Increased risk of convulsions
Iron Formation of non-absorbable complexes
Magnesium Formation of non-absorbable complexes
Magnesium oxide Formation of non-absorbable complexes
Oxtriphylline The quinolone increases the effect of theophylline
Sucralfate Formation of non-absorbable complexes
Theophylline The quinolone increases the effect of theophylline
Warfarin The quinolone increases the anticoagulant effect
Zinc Formation of non-absorbable complexes
Food Interactions
  • Avoid high doses of caffeine.
  • Take on an empty stomach. Drink liberally.
Pathways Not Available
General References
  1. Goldstein EJ: Norfloxacin, a fluoroquinolone antibacterial agent. Classification, mechanism of action, and in vitro activity. Am J Med. 1987 Jun 26;82(6B):3-17. [PubMed Link Image]
  2. Drugs.com Link Image
  3. Wikipedia Link Image
  4. RxList Link Image
  5. PDRhealth Link Image
Organisms Affected
  • Enteric bacteria and other eubacteria
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 1A2 (CYP1A2)
Targets
  1. DNA gyrase subunit A
  2. DNA topoisomerase 4 subunit A
  3. DNA topoisomerase 2-alpha
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 1A2 (CYP1A2)
Enzyme 1 Gene Name CYP1A2
Enzyme 1 SwissProt ID P05177 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >P05177|CP1A2_HUMAN Cytochrome P450 1A2 - Homo sapiens (Human). 
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKN
PHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDG
QSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELM
AGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFP
ILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGN
LIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLS
DRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPEL
WEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLE
FSVPPGVKVDLTPIYGLTMKHARCEHVQARRFSIN
Drug Target 1 [top]
Target 1 ID 404
Target 1 Name DNA gyrase subunit A
Target 1 Synonyms
  1. EC 5.99.1.3
Target 1 Gene Name gyrA
Target 1 Protein Sequence >DNA gyrase subunit A 
MTDSIQSSITPVNIEEELKSSYLDYAMSVIVGRALPDVRDGLKPVHRRVLFSMDREGNTA
NKKYVKSARVVGDVIGKYHPHGDSAVYDTIVRMAQPFSLRYMLVDGQGNFGSIDGDAPAA
MRYTEVRMQKITQALLTDLDKETVNFSPNYDGELMIPDVLPTRIPALLANGSSGIAVGMA
TNIPPHNLNEVLNGCLAYIDKNEITIDELMQHIPGPDFPTAALINGRKGIEEAYRTGRGK
VYVRARATVETNEKGREQIIVSELPYQVNKAKLVEKIAELIREKKIEGISNITDLSNKEG
IRIEIDIKRDAVGEVVLNHLYSLTQMQVTFGINMVALDHGQPRLFNLKEIIEAFVLHRRE
VVTRRSIFELRKARERTHILEGLAVARSNIDEMIAIIRNSKNREEAATSISSRSWTLHSD
IINLLDASARPDELEENLGIQGEQYYLSPAQVNAILELRLHRLTGIAFEEVIKEYEELLV
KIADLLHILSSAERLMEVIREELEEVKAQFGDDRLTEITAASGDIDLEDLIAQEDVVVTL
SHEGYVKYQPLTDYEAQRRGGKGKSATKMKEEDFIEKLLVANTHDTILCFSSRGRLYWLK
VYQLPQASRGARGRPIVNILPLQENERITAILPVSAYEEDKFVVMATAGGIVKKIALTEF
SRPRSNGIIALNLRDEDELIGVDITDGSNEIMLFSSQGRVVRFAENAVRAMGRLATGVRG
IKLALTNDISDDESAVEIEDISDDNAEASLDLNIDKVVSLVVPKGEGAILTATQNGYGKR
TQLSEYPTKSRNTKGVISIKVSERNGKVVAATQVEETDQIMLITDAGTLVRTRVSEVSIV
GRNTQGVRLIRTADDEHVVSLERVCDADEDDSLEESSSEE
Target 1 Number of Residues 894
Target 1 Molecular Weight 97820
Target 1 Theoretical pI 4.85
Target 1 GO Classification
Function
nucleotide binding
purine nucleotide binding
adenyl nucleotide binding
ATP binding
DNA topoisomerase (ATP-hydrolyzing) activity
DNA topoisomerase activity
DNA topoisomerase (ATP-hydrolyzing) activity
binding
nucleic acid binding
DNA binding
Process
DNA replication
DNA-dependent DNA replication
DNA unwinding during replication
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
DNA metabolism
DNA topological change
Component
organelle
non-membrane-bound organelle
intracellular non-membrane-bound organelle
chromosome
Target 1 General Function Replication, recombination and repair
Target 1 Specific Function DNA gyrase negatively supercoils closed circular double- stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings
Target 1 Pathways Not Available
Target 1 Reactions
  • ATP-dependent breakage, passage and rejoining of double-stranded DNA INHIBITOR Coumermycin A1; GRI22222X; Nalidixic acid; Novobiocin; Ciprofloxacin
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 1574722 Link Image
Target 1 UniProtKB/Swiss-Prot ID P43700 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name GYRA_HAEIN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Cytoplasmic
Target 1 Gene Sequence >2643 bp 
TTATTCTTCAGAACTGCTTTCTTCCAAAGAATCATCTTCATCTGCATCACAAACACGTTC
TAAACTTACTACGTGTTCATCATCGGCAGTACGAATTAAGCGAACACCTTGCGTGTTACG
CCCTACAATGCTCACTTCGCTTACGCGTGTGCGAACAAGGGTTCCTGCATCAGTGATCAA
CATAATTTGGTCTGTTTCTTCTACTTGAGTTGCGGCAACGACTTTACCATTGCGTTCACT
CACTTTAATCGAAATCACACCTTTTGTATTACGTGATTTAGTTGGGTATTCACTTAATTG
TGTGCGTTTTCCGTAGCCGTTTTGCGTTGCGGTTAAAATTGCCCCTTCACCTTTTGGCAC
AACGAGCGAGACCACTTTATCGATATTTAAGTCTAATGATGCTTCAGCGTTGTCATCAGA
AATATCTTCAATTTCTACCGCACTTTCATCGTCAGAAATATCGTTTGTTAAAGCCAGTTT
GATACCGCGAACACCTGTTGCTAAACGCCCCATCGCACGCACGGCATTTTCAGCAAAACG
CACCACGCGACCTTGTGATGAGAACAACATAATTTCGTTGCTGCCATCAGTAATATCCAC
GCCGATTAATTCATCTTCGTCACGTAAATTCAATGCGATGATACCGTTTGAACGTGGACG
GCTAAATTCGGTTAAGGCGATTTTCTTCACAATACCGCCAGCAGTTGCCATGACTACGAA
TTTATCTTCTTCGTAAGCAGAAACTGGCAAGATTGCAGTAATACGTTCGTTTTCTTGTAA
CGGAAGAATATTCACAATTGGACGACCGCGTGCGCCACGGCTCGCTTGCGGAAGTTGATA
TACTTTCAACCAATATAAACGACCACGGCTAGAGAAGCAGAGGATGGTATCGTGAGTATT
TGCTACCAGTAATTTTTCGATGAAATCTTCTTCTTTCATCTTCGTTGCAGATTTGCCTTT
ACCGCCACGGCGTTGTGCTTCATAGTCAGTCAGTGGTTGGTATTTCACATAACCTTCGTG
AGAAAGCGTCACAACCACGTCTTCTTGTGCGATTAAATCTTCTAAATCAATATCGCCAGA
AGCAGCGGTAATTTCAGTTAAACGATCATCACCAAATTGTGCTTTTACTTCTTCCAATTC
TTCACGAATTACTTCCATTAAACGTTCTGCACTACTTAAAATATGAAGAAGATCCGCAAT
TTTAACTAATAATTCTTCATATTCTTTTATAACTTCTTCAAACGCAATGCCCGTTAAACG
GTGTAAGCGAAGTTCTAGAATTGCGTTTACTTGCGCTGGCGATAAGTAATATTGTTCGCC
TTGAATACCAAGATTTTCTTCTAACTCATCAGGACGAGCAGAAGCATCAAGAAGATTAAT
AATATCGCTATGTAACGTCCAAGAGCGTGAACTGATTGATGTTGCGGCTTCTTCACGGTT
TTTAGAGTTACGAATGATCGCAATCATTTCATCGATATTAGAACGAGCAACCGCTAAACC
TTCCAAAATATGCGTACGTTCACGTGCTTTGCGAAGCTCAAAGATAGAACGACGTGTAAC
CACTTCACGGCGGTGTAAAACAAAGGCTTCAATAATTTCTTTAAGATTAAATAAACGTGG
CTGACCGTGATCCAATGCCACCATATTGATACCAAAGGTCACTTGCATTTGAGTGAGTGA
GTAAAGATGGTTTAATACCACTTCCCCCACTGCATCACGTTTAATATCAATTTCAATACG
GATCCCTTCTTTATTTGAAAGGTCAGTAATATTGCTGATACCTTCGATTTTTTTCTCGCG
AATTAATTCGGCGATTTTCTCGACTAATTTTGCTTTATTTACTTGGTATGGCAATTCAGA
CACGATAATTTGCTCGCGTCCTTTTTCGTTGGTTTCTACCGTTGCACGAGCACGAACATA
CACTTTACCACGACCAGTGCGATAGGCCTCTTCAATCCCTTTACGACCATTAATTAACGC
AGCCGTTGGGAAGTCAGGCCCTGGAATATGTTGCATTAATTCATCAATGGTAATTTCATT
TTTGTCAATATAAGCCAAACAACCATTTAATACTTCGTTTAAGTTGTGAGGGGGAATGTT
AGTTGCCATCCCCACCGCAATACCAGAAGAACCATTTGCTAACAGTGCTGGAATACGAGT
CGGCAATACATCTGGAATCATTAATTCGCCATCATAGTTTGGCGAGAAATTGACGGTTTC
TTTATCCAAATCCGTGAGCAATGCTTGCGTAATTTTTTGCATACGTACTTCGGTATAACG
CATTGCAGCTGGCGCATCACCATCAATTGAACCAAAGTTACCTTGCCCATCAACCAACAT
ATAGCGAAGTGAGAAGGGTTGTGCCATACGAACGATGGTATCGTACACGGCGGAGTCACC
ATGCGGGTGATATTTACCGATTACATCACCCACAACACGCGCTGATTTTACGTATTTTTT
ATTGGCGGTATTGCCTTCGCGATCCATTGAGAATAGTACGCGGCGGTGAACAGGTTTTAA
ACCATCTCGAACGTCAGGTAATGCACGCCCAACGATAACCGACATCGCGTAGTCAAGGTA
GGAAGATTTAAGTTCTTCTTCGATATTGACAGGGGTGATAGATGATTGGATTGAATCCGT
CAT
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb JF, Dougherty BA, Merrick JM, et al.: Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995 Jul 28;269(5223):496-512. [PubMed Link Image]
Target 1 Drug References
  1. Hombrouck C, Capmau ML, Moreau N: Overexpression, purification and photoaffinity labeling with a 3H-analogue of norfloxacin, of the GyrA and GyrB subunits of the DNA gyrase. Cell Mol Biol (Noisy-le-grand). 1999 May;45(3):347-52. [PubMed Link Image]
  2. 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]
  3. 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]
  4. Hooper DC: Quinolone mode of action--new aspects. Drugs. 1993;45 Suppl 3:8-14. [PubMed Link Image]
  5. Fukuda H, Hori S, Hiramatsu K: Antibacterial activity of gatifloxacin (AM-1155, CG5501, BMS-206584), a newly developed fluoroquinolone, against sequentially acquired quinolone-resistant mutants and the norA transformant of Staphylococcus aureus. Antimicrob Agents Chemother. 1998 Aug;42(8):1917-22. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 477
Target 2 Name DNA topoisomerase 4 subunit A
Target 2 Synonyms
  1. EC 5.99.1.-
  2. Topoisomerase IV subunit A
Target 2 Gene Name parC
Target 2 Protein Sequence >DNA topoisomerase 4 subunit A 
MTNINYEGIEQMPLRTFTEKAYLNYSMYVIMDRALPFIGDGLKPVQRRIVYAMSELGLNA
TAKYKKSARTVGDVLGKFHPHGDSACYEAMVLMAQPFSYRYPLVDGQGNWGAPDDPKSFA
AMRYTESRLSKISEILLNELGQGTVDYQPNFDGTLAEPQYLPARLPHILLNGTTGIAVGM
ATDIPPHNINEIADAAVMLLDNPKAGLDDVLEIVQGPDFPTEAEIISPKSEIRKIYEQGR
GSIKMRATWKKEDGEIIISALPHQSSPSKVIAQIAEQMTAKKLPMLEDIRDEADHENPIR
IVLVPRSNRVDTDALMAHLFATTDLEKSYRVNMNMIGLDHKPAVKGLLEILNEWLDFRRT
TVTRRLQYRLDKVLSRLHILEGLMIAFLNIDEVIEIIRHEDDPKAELMARFNLSDEQADA
ILNLRLRHLAKLEENQLKAEQDELEKERLNLEAILGSERRLNTLIKKEIQEDAKKYANPR
MSQLVEREEAKMISESDMTPAEPVTVILSEMGWVRCAKGHDIDPKSLSYKAGDSYLAHAC
GKSNQAVVFIDSTGRSYALDPLSLPSARSQGEPLTGKLNLPTGATIEYVVMASEQQELLM
ASDAGYGFICKFEDLIARNKAGKALISLPENAKVLKPKTLINSTALVVAITSAGRMLIFP
AQDLPVLSKGKGNKMITIPAANAKDRSELLTKLLLISDQASLEFYSGKRKIVLKPEDLQK
FRAERGRKGSTLPRGLHTNLEIMVIEP
Target 2 Number of Residues 759
Target 2 Molecular Weight 83368
Target 2 Theoretical pI 6.42
Target 2 GO Classification
Function
DNA topoisomerase (ATP-hydrolyzing) activity
nucleotide binding
purine nucleotide binding
adenyl nucleotide binding
ATP binding
DNA topoisomerase (ATP-hydrolyzing) activity
DNA topoisomerase activity
binding
nucleic acid binding
DNA binding
Process
DNA replication
DNA-dependent DNA replication
DNA unwinding during replication
DNA topological change
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
DNA metabolism
Component
organelle
non-membrane-bound organelle
intracellular non-membrane-bound organelle
chromosome
Target 2 General Function Replication, recombination and repair
Target 2 Specific Function Topoisomerase IV is essential for chromosome segregation. It has relaxation of supercoiled DNA activity. Performs the decatenation events required during the replication of a circular DNA molecule
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Essential
Target 2 GenBank ID Protein 1574370 Link Image
Target 2 UniProtKB/Swiss-Prot ID P43702 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name PARC_HAEIN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Bacterial cell membrane
  • peripheral membrane protein
Target 2 Gene Sequence >2244 bp 
ATGACAAATATCAACTATGAAGGCATTGAGCAAATGCCTCTACGCACCTTCACTGAAAAG
GCTTATCTCAACTATTCTATGTATGTCATCATGGATCGTGCGTTGCCTTTTATCGGTGAT
GGTTTAAAACCCGTTCAACGTCGTATTGTATATGCGATGTCTGAACTTGGCTTAAATGCC
ACGGCAAAATACAAAAAATCTGCTCGTACCGTCGGTGATGTACTCGGTAAATTCCATCCA
CATGGTGACAGTGCTTGTTATGAAGCTATGGTGTTAATGGCACAACCCTTCTCTTATCGT
TATCCACTTGTAGATGGTCAAGGTAACTGGGGGGCACCAGATGATCCAAAATCCTTCGCA
GCCATGCGTTATACGGAATCTCGCCTATCTAAAATCTCTGAAATCTTGTTGAATGAACTC
GGACAAGGAACAGTAGATTATCAACCAAACTTTGATGGAACCTTGGCTGAACCACAATAT
TTACCTGCTCGTTTACCGCATATTTTATTGAACGGCACAACAGGTATTGCGGTGGGGATG
GCCACAGATATTCCACCACACAATATTAACGAAATTGCTGATGCGGCAGTAATGTTGCTA
GATAATCCTAAAGCGGGATTAGATGATGTACTTGAAATTGTTCAAGGCCCAGATTTTCCA
ACAGAAGCGGAAATTATTTCGCCAAAATCAGAAATTCGTAAAATTTATGAGCAAGGTCGT
GGCTCAATAAAAATGCGTGCAACTTGGAAAAAAGAAGACGGTGAAATTATTATTTCAGCG
CTTCCACATCAATCTTCGCCATCCAAAGTCATTGCACAAATAGCCGAACAAATGACGGCA
AAAAAACTGCCAATGCTAGAAGATATTCGAGATGAAGCCGATCACGAAAATCCAATTCGC
ATTGTGCTAGTTCCTCGCTCAAATCGCGTCGATACTGATGCCTTAATGGCACATTTATTT
GCGACCACAGATCTTGAAAAAAGCTACCGTGTAAATATGAATATGATCGGGCTTGATCAT
AAACCAGCGGTAAAAGGCTTATTAGAAATCTTAAATGAATGGCTTGACTTCCGTCGCACA
ACGGTCACTCGTCGCCTTCAATATCGCCTAGATAAAGTGCTCTCTCGCTTGCATATTTTA
GAAGGCTTGATGATAGCCTTTTTAAATATTGATGAAGTTATCGAAATTATACGCCACGAA
GATGATCCAAAAGCAGAGCTTATGGCACGCTTTAATTTAAGCGATGAACAAGCCGATGCC
ATTTTAAATTTACGCTTACGTCATTTAGCGAAATTAGAAGAAAACCAACTCAAAGCAGAA
CAAGATGAACTTGAAAAAGAGCGGTTAAATTTAGAAGCAATTTTAGGATCAGAACGCCGT
TTGAATACGCTTATCAAAAAAGAAATTCAAGAAGATGCGAAAAAATATGCCAATCCACGT
ATGTCTCAACTGGTCGAACGTGAAGAAGCCAAAATGATCTCTGAAAGTGATATGACACCA
GCAGAACCAGTTACTGTCATCTTATCAGAAATGGGCTGGGTACGTTGTGCAAAAGGACAC
GATATTGATCCTAAATCATTAAGCTACAAAGCTGGTGATAGCTATCTAGCTCACGCTTGT
GGCAAAAGTAATCAAGCCGTTGTATTCATTGATAGCACGGGGCGGAGTTATGCACTCGAT
CCGCTTTCCTTGCCTTCCGCTCGCTCCCAAGGCGAACCACTTACAGGTAAACTCAATTTA
CCCACTGGTGCGACCATTGAATATGTTGTAATGGCCAGCGAACAGCAAGAATTATTGATG
GCTTCTGATGCAGGATATGGTTTTATTTGTAAATTTGAAGATTTAATTGCACGTAACAAG
GCTGGAAAAGCCTTGATTTCTTTACCAGAAAATGCCAAAGTGTTGAAGCCTAAAACATTG
ATAAATTCTACCGCACTTGTTGTCGCAATCACATCAGCAGGCAGAATGTTGATTTTTCCA
GCACAGGATTTACCGGTATTATCAAAAGGTAAAGGCAATAAAATGATCACTATTCCCGCA
GCGAATGCAAAAGATCGTAGCGAACTATTGACAAAATTATTGCTTATTTCAGATCAAGCA
AGTCTTGAATTTTATTCTGGAAAACGAAAAATTGTATTAAAACCAGAAGATCTGCAAAAG
TTCCGCGCAGAACGAGGCAGAAAAGGTTCGACATTACCACGTGGATTACATACCAATCTT
GAAATTATGGTAATCGAGCCGTAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID Not Available
Target 2 GenAtlas ID Not Available
Target 2 HGNC ID Not Available
Target 2 Chromosome Location Not Available
Target 2 Locus Not Available
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb JF, Dougherty BA, Merrick JM, et al.: Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995 Jul 28;269(5223):496-512. [PubMed Link Image]
Target 2 Drug References
  1. Rafii F, Park M, Novak JS: Alterations in DNA gyrase and topoisomerase IV in resistant mutants of Clostridium perfringens found after in vitro treatment with fluoroquinolones. Antimicrob Agents Chemother. 2005 Feb;49(2):488-92. [PubMed Link Image]
  2. Oyamada Y, Ito H, Fujimoto K, Asada R, Niga T, Okamoto R, Inoue M, Yamagishi J: Combination of known and unknown mechanisms confers high-level resistance to fluoroquinolones in Enterococcus faecium. J Med Microbiol. 2006 Jun;55(Pt 6):729-36. [PubMed Link Image]
  3. Vila J, Sanchez-Cespedes J, Sierra JM, Piqueras M, Nicolas E, Freixas J, Giralt E: Antibacterial evaluation of a collection of norfloxacin and ciprofloxacin derivatives against multiresistant bacteria. Int J Antimicrob Agents. 2006 Jul;28(1):19-24. Epub 2006 Jun 14. [PubMed Link Image]
  4. 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]
  5. 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 817
Target 3 Name DNA topoisomerase 2-alpha
Target 3 Synonyms
  1. DNA topoisomerase II, alpha isozyme
  2. EC 5.99.1.3
Target 3 Gene Name TOP2A
Target 3 Protein Sequence >DNA topoisomerase 2-alpha 
MEVSPLQPVNENMQVNKIKKNEDAKKRLSVERIYQKKTQLEHILLRPDTYIGSVELVTQQ
MWVYDEDVGINYREVTFVPGLYKIFDEILVNAADNKQRDPKMSCIRVTIDPENNLISIWN
NGKGIPVVEHKVEKMYVPALIFGQLLTSSNYDDDEKKVTGGRNGYGAKLCNIFSTKFTVE
TASREYKKMFKQTWMDNMGRAGEMELKPFNGEDYTCITFQPDLSKFKMQSLDKDIVALMV
RRAYDIAGSTKDVKVFLNGNKLPVKGFRSYVDMYLKDKLDETGNSLKVIHEQVNHRWEVC
LTMSEKGFQQISFVNSIATSKGGRHVDYVADQIVTKLVDVVKKKNKGGVAVKAHQVKNHM
WIFVNALIENPTFDSQTKENMTLQPKSFGSTCQLSEKFIKAAIGCGIVESILNWVKFKAQ
VQLNKKCSAVKHNRIKGIPKLDDANDAGGRNSTECTLILTEGDSAKTLAVSGLGVVGRDK
YGVFPLRGKILNVREASHKQIMENAEINNIIKIVGLQYKKNYEDEDSLKTLRYGKIMIMT
DQDQDGSHIKGLLINFIHHNWPSLLRHRFLEEFITPIVKVSKNKQEMAFYSLPEFEEWKS
STPNHKKWKVKYYKGLGTSTSKEAKEYFADMKRHRIQFKYSGPEDDAAISLAFSKKQIDD
RKEWLTNFMEDRRQRKLLGLPEDYLYGQTTTYLTYNDFINKELILFSNSDNERSIPSMVD
GLKPGQRKVLFTCFKRNDKREVKVAQLAGSVAEMSSYHHGEMSLMMTIINLAQNFVGSNN
LNLLQPIGQFGTRLHGGKDSASPRYIFTMLSSLARLLFPPKDDHTLKFLYDDNQRVEPEW
YIPIIPMVLINGAEGIGTGWSCKIPNFDVREIVNNIRRLMDGEEPLPMLPSYKNFKGTIE
ELAPNQYVISGEVAILNSTTIEISELPVRTWTQTYKEQVLEPMLNGTEKTPPLITDYREY
HTDTTVKFVVKMTEEKLAEAERVGLHKVFKLQTSLTCNSMVLFDHVGCLKKYDTVLDILR
DFFELRLKYYGLRKEWLLGMLGAESAKLNNQARFILEKIDGKIIIENKPKKELIKVLIQR
GYDSDPVKAWKEAQQKVPDEEENEESDNEKETEKSDSVTDSGPTFNYLLDMPLWYLTKEK
KDELCRLRNEKEQELDTLKRKSPSDLWKEDLATFIEELEAVEAKEKQDEQVGLPGKGGKA
KGKKTQMAEVLPSPRGQRVIPRITIEMKAEAEKKNKKKIKNENTEGSPQEDGVELEGLKQ
RLEKKQKREPGTKTKKQTTLAFKPIKKGKKRNPWSDSESDRSSDESNFDVPPRETEPRRA
ATKTKFTMDLDSDEDFSDFDEKTDDEDFVPSDASPPKTKTSPKLSNKELKPQKSVVSDLE
ADDVKGSVPLSSSPPATHFPDETEITNPVPKKNVTVKKTAAKSQSSTSTTGAKKRAAPKG
TKRDPALNSGVSQKPDPAKTKNRRKRKPSTSDDSDSNFEKIVSKAVTSKKSKGESDDFHM
DFDSAVAPRAKSVRAKKPIKYLEESDEDDLF
Target 3 Number of Residues 1556
Target 3 Molecular Weight 174387
Target 3 Theoretical pI 9.17
Target 3 GO Classification
Function
DNA topoisomerase (ATP-hydrolyzing) activity
DNA topoisomerase activity
DNA topoisomerase (ATP-hydrolyzing) activity
nucleic acid binding
DNA binding
binding
nucleotide binding
purine nucleotide binding
adenyl nucleotide binding
ATP binding
Process
DNA topological change
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
DNA metabolism
Component
Not Available
Target 3 General Function Replication, recombination and repair
Target 3 Specific Function Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks
Target 3 Pathways Not Available
Target 3 Reactions
  • ATP-dependent breakage, passage and rejoining of double-stranded DNA INHIBITOR Coumermycin A1; GRI22222X; Nalidixic acid; Novobiocin; Ciprofloxacin
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 292830 Link Image
Target 3 UniProtKB/Swiss-Prot ID P11388 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name TOP2A_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Cytoplasm. Nucleus
  • nucleoplasm. Generally located in the nucleoplasm
Target 3 Gene Sequence >4596 bp 
ATGGAAGTGTCACCATTGCAGCCTGTAAATGAAAATATGCAAGTCAACAAAATAAAGAAA
AATGAAGATGCTAAGAAAAGACTGTCTGTTGAAAGAATCTATCAAAAGAAAACACAATTG
GAACATATTTTGCTCCGCCCAGACACCTACATTGGTTCTGTGGAATTAGTGACCCAGCAA
ATGTGGGTTTACGATGAAGATGTTGGCATTAACTATAGGGAAGTCACTTTTGTTCCTGGT
TTGTACAAAATCTTTGATGAGATTCTAGTTAATGCTGCGGACAACAAACAAAGGGACCCA
AAAATGTCTTGTATTAGAGTCACAATTGATCCGGAAAACAATTTAATTAGTATATGGAAT
AATGGAAAAGGTATTCCTGTTGTTGAACACAAAGTTGAAAAGATGTATGTCCCAGCTCTC
ATATTTGGACAGCTCCTAACTTCTAGTAACTATGATGATGATGAAAAGAAAGTGACAGGT
GGTCGAAATGGCTATGGAGCCAAATTGTGTAACATATTCAGTACCAAATTTACTGTGGAA
ACAGCCAGTAGAGAATACAAGAAAATGTTCAAACAGACATGGATGGATAATATGGGAAGA
GCTGGTGAGATGGAACTCAAGCCCTTCAATGGAGAAGATTATACATGTATCACCTTTCAG
CCTGATTTGTCTAAGTTTAAAATGCAAAGCCTGGACAAAGATATTGTTGCACTAATGGTC
AGAAGAGCATATGATATTGCTGGATCCACCAAAGATGTCAAAGTCTTTCTTAATGGAAAT
AAACTGCCAGTAAAAGGATTTCGTAGTTATGTGGACATGTATTTGAAGGACAAGTTGGAT
GAAACTGGTAACTCCTTGAAAGTAATACATGAACAAGTAAACCACAGGTGGGAAGTGTGT
TTAACTATGAGTGAAAAAGGCTTTCAGCAAATTAGCTTTGTCAACAGCATTGCTACATCC
AAGGGTGGCAGACATGTTGATTATGTAGCTGATCAGATTGTGACTAAACTTGTTGATGTT
GTGAAGAAGAAGAACAAGGGTGGTGTTGCAGTAAAAGCACATCAGGTGAAAAATCACATG
TGGATTTTTGTAAATGCCTTAATTGAAAACCCAACCTTTGACTCTCAGACAAAAGAAAAC
ATGACTTTACAACCCAAGAGCTTTGGATCAACATGCCAATTGAGTGAAAAATTTATCAAA
GCTGCCATTGGCTGTGGTATTGTAGAAAGCATACTAAACTGGGTGAAGTTTAAGGCCCAA
GTCCAGTTAAACAAGAAGTGTTCAGCTGTAAAACATAATAGAATCAAGGGAATTCCCAAA
CTCGATGATGCCAATGATGCAGGGGGCCGAAACTCCACTGAGTGTACGCTTATCCTGACT
GAGGGAGATTCAGCCAAAACTTTGGCTGTTTCAGGCCTTGGTGTGGTTGGGAGAGACAAA
TATGGGGTTTTCCCTCTTAGAGGAAAAATACTCAATGTTCGAGAAGCTTCTCATAAGCAG
ATCATGGAAAATGCTGAGATTAACAATATCATCAAGATTGTGGGTCTTCAGTACAAGAAA
AACTATGAAGATGAAGATTCATTGAAGACGCTTCGTTATGGGAAGATAATGATTATGACA
GATCAGGACCAAGATGGTTCCCACATCAAAGGCTTGCTGATTAATTTTATCCATCACAAC
TGGCCCTCTCTTCTGCGACATCGTTTTCTGGAGGAATTTATCACTCCCATTGTAAAGGTA
TCTAAAAACAAGCAAGAAATGGCATTTTACAGCCTTCCTGAATTTGAAGAGTGGAAGAGT
TCTACTCCAAATCATAAAAAATGGAAAGTCAAATATTACAAAGGTTTGGGCACCAGCACA
TCAAAGGAAGCTAAAGAATACTTTGCAGATATGAAAAGACATCGTATCCAGTTCAAATAT
TCTGGTCCTGAAGATGATGCTGCTATCAGCCTGGCCTTTAGCAAAAAACAGATAGATGAT
CGAAAGGAATGGTTAACTAATTTCATGGAGGATAGAAGACAACGAAAGTTACTTGGGCTT
CCTGAGGATTACTTGTATGGACAAACTACCACATATCTGACATATAATGACTTCATCAAC
AAGGAACTTATCTTGTTCTCAAATTCTGATAACGAGAGATCTATCCCTTCTATGGTGGAT
GGTTTGAAACCAGGTCAGAGAAAGGTTTTGTTTACTTGCTTCAAACGGAATGACAAGCGA
GAAGTAAAGGTTGCCCAATTAGCTGGATCAGTGGCTGAAATGTCTTCTTATCATCATGGT
GAGATGTCACTAATGATGACCATTATCAATTTGGCTCAGAATTTTGTGGGTAGCAATAAT
CTAAACCTCTTGCAGCCCATTGGTCAGTTTGGTACCAGGCTACATGGTGGCAAGGATTCT
GCTAGTCCACGATACATCTTTACAATGCTCAGCTCTTTGGCTCGATTGTTATTTCCACCA
AAAGATGATCACACGTTGAAGTTTTTATATGATGACAACCAGCGTGTTGAGCCTGAATGG
TACATTCCTATTATTCCCATGGTGCTGATAAATGGTGCTGAAGGAATCGGTACTGGGTGG
TCCTGCAAAATCCCCAACTTTGATGTGCGTGAAATTGTAAATAACATCAGGCGTTTGATG
GATGGAGAAGAACCTTTGCCAATGCTTCCAAGTTACAAGAACTTCAAGGGTACTATTGAA
GAACTGGCTCCAAATCAATATGTGATTAGTGGTGAAGTAGCTATTCTTAATTCTACAACC
ATTGAAATCTCAGAGCTTCCCGTCAGAACATGGACCCAGACATACAAAGAACAAGTTCTA
GAACCCATGTTGAATGGCACCGAGAAGACACCTCCTCTCATAACAGACTATAGGGAATAC
CATACAGATACCACTGTGAAATTTGTTGTGAAGATGACTGAAGAAAAACTGGCAGAGGCA
GAGAGAGTTGGACTACACAAAGTCTTCAAACTCCAAACTAGTCTCACATGCAACTCTATG
GTGCTTTTTGACCACGTAGGCTGTTTAAAGAAATATGACACGGTGTTGGATATTCTAAGA
GACTTTTTTGAACTCAGACTTAAATATTATGGATTAAGAAAAGAATGGCTCCTAGGAATG
CTTGGTGCTGAATCTGCTAAACTGAATAATCAGGCTCGCTTTATCTTAGAGAAAATAGAT
GGCAAAATAATCATTGAAAATAAGCCTAAGAAAGAATTAATTAAAGTTCTGATTCAGAGG
GGATATGATTCGGATCCTGTGAAGGCCTGGAAAGAAGCCCAGCAAAAGGTTCCAGATGAA
GAAGAAAATGAAGAGAGTGACAACGAAAAGGAAACTGAAAAGAGTGACTCCGTAACAGAT
TCTGGACCAACCTTCAACTATCTTCTTGATATGCCCCTTTGGTATTTAACCAAGGAAAAG
AAAGATGAACTCTGCAGGCTAAGAAATGAAAAAGAACAAGAGCTGGACACATTAAAAAGA
AAGAGTCCATCAGATTTGTGGAAAGAAGACTTGGCTACATTTATTGAAGAATTGGAGGCT
GTTGAAGCCAAGGAAAAACAAGATGAACAAGTCGGACTTCCTGGGAAAGGGGGGAAGGCC
AAGGGGAAAAAAACACAAATGGCTGAAGTTTTGCCTTCTCCGCGTGGTCAAAGAGTCATT
CCACGAATAACCATAGAAATGAAAGCAGAGGCAGAAAAGAAAAATAAAAAGAAAATTAAG
AATGAAAATACTGAAGGAAGCCCTCAAGAAGATGGTGTGGAACTAGAAGGCCTAAAACAA
AGATTAGAAAAGAAACAGAAAAGAGAACCAGGTACAAAGACAAAGAAACAAACTACATTG
GCATTTAAGCCAATCAAAAAAGGAAAGAAGAGAAATCCCTGGCCTGATTCAGAATCAGAT
AGGAGCAGTGACGAAAGTAATTTTGATGTCCCTCCACGAGAAACAGAGCCACGGAGAGCA
GCAACAAAAACAAAATTCACAATGGATTTGGATTCAGATGAAGATTTCTCAGATTTTGAT
GAAAAAACTGATGATGAAGATTTTGTCCCATCAGATGCTAGTCCACCTAAGACCAAAACT
TCCCCAAAACTTAGTAACAAAGAACTGAAACCACAGAAAAGTGTCGTGTCAGACCTTGAA
GCTGATGATGTTAAGGGCAGTGTACCACTGTCTTCAAGCCCTCCTGCTACACATTTCCCA
GATGAAACTGAAATTACAAACCCAGTTCCTAAAAAGAATGTGACAGTGAAGAAGACAGCA
GCAAAAAGTCAGTCTTCCACCTCCACTACCGGTGCCAAAAAAAGGGCTGCCCCAAAAGGA
ACTAAAAGGGATCCAGCTTTGAATTCTGGTGTCTCTCAAAAGCCTGATCCTGCCAAAACC
AAGAATCGCCGCAAAAGGAAGCCATCCACTTCTGATGATTCTGACTCTAATTTTGAGAAA
ATTGTTTCGAAAGCAGTCACAAGCAAGAAATCCAAGGGGGAGAGTGATGACTTCCATATG
GACTTTGACTCAGCTGTGGCTCCTCGGGCAAAATCTGTACGGGCAAAGAAACCTATAAAG
TACCTGGAAGAGTCAGATGAAGATGATCTGTTTTAA
Target 3 GenBank Gene ID
Target 3 GeneCard ID TOP2A Link Image
Target 3 GenAtlas ID TOP2A Link Image
Target 3 HGNC ID HGNC:11989 Link Image
Target 3 Chromosome Location 17
Target 3 Locus 17q21-q22
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Sng JH, Heaton VJ, Bell M, Maini P, Austin CA, Fisher LM: Molecular cloning and characterization of the human topoisomerase IIalpha and IIbeta genes: evidence for isoform evolution through gene duplication. Biochim Biophys Acta. 1999 Mar 19;1444(3):395-406. [PubMed Link Image]
  2. Escargueil AE, Plisov SY, Filhol O, Cochet C, Larsen AK: Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase CK2 creates the MPM-2 phosphoepitope on Ser-1469. J Biol Chem. 2000 Nov 3;275(44):34710-8. [PubMed Link Image]
  3. Mirski SE, Bielawski JC, Cole SP: Identification of functional nuclear export sequences in human topoisomerase IIalpha and beta. Biochem Biophys Res Commun. 2003 Jul 11;306(4):905-11. [PubMed Link Image]
  4. Hinds M, Deisseroth K, Mayes J, Altschuler E, Jansen R, Ledley FD, Zwelling LA: Identification of a point mutation in the topoisomerase II gene from a human leukemia cell line containing an amsacrine-resistant form of topoisomerase II. Cancer Res. 1991 Sep 1;51(17):4729-31. [PubMed Link Image]
  5. Bugg BY, Danks MK, Beck WT, Suttle DP: Expression of a mutant DNA topoisomerase II in CCRF-CEM human leukemic cells selected for resistance to teniposide. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7654-8. [PubMed Link Image]
  6. Tsai-Pflugfelder M, Liu LF, Liu AA, Tewey KM, Whang-Peng J, Knutsen T, Huebner K, Croce CM, Wang JC: Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7177-81. [PubMed Link Image]
  7. Wasserman RA, Austin CA, Fisher LM, Wang JC: Use of yeast in the study of anticancer drugs targeting DNA topoisomerases: expression of a functional recombinant human DNA topoisomerase II alpha in yeast. Cancer Res. 1993 Aug 1;53(15):3591-6. [PubMed Link Image]
  8. Lang AJ, Mirski SE, Cummings HJ, Yu Q, Gerlach JH, Cole SP: Structural organization of the human TOP2A and TOP2B genes. Gene. 1998 Oct 23;221(2):255-66. [PubMed Link Image]
Target 3 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]

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.