| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-02-19 16:04:11 |
| Primary Accession Number |
DB01165 |
| Secondary Accession Number |
|
| Name |
Ofloxacin |
| Drug Type |
|
| Description |
A synthetic fluoroquinolone (fluoroquinolones) antibacterial agent that inhibits the supercoiling activity of bacterial DNA gyrase, halting DNA replication. [PubChem] |
| Synonyms |
Not Available |
| Brand Names |
- Akilen
- Baccidal
- Bactocin
- Danoflox
- Effexin
- Exocin
- Exocine
- Flobacin
- Flodemex
- Flotavid
- Flovid
- Floxal
- Floxil
- Floxin
- Floxstat
- Fugacin
- Inoflox
- Kinflocin
- Kinoxacin
- Liflox
- Loxinter
- Marfloxacin
- Medofloxine
- Mergexin
- Novecin
- Nufafloqo
- O-Flox
- Obide
- Occidal
- Ofcin
- Oflin
- Oflocee
- Oflocet
- Oflocin
- Oflodal
- Oflodex
- Oflodura
- Oflox
- Ofloxin
- Ofus
- Onexacin
- Operan
- Orocin
- Otonil
- Pharflox
- Praxin
- Puiritol
- Qinolon
- Qipro
- Quinolon
- Quotavil
- Rilox
- Sinflo
- Tabrin
- Taravid
- Tariflox
- Tarivid
- Telbit
- Tructum
- Uro Tarivid
- Viotisone
- Zanocin
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
(+/-)-9-fluoro-2, 3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1, 2, 3-de]-1, 4-benzoxazine-6-carboxylic acid |
| Chemical Formula |
C18H20FN3O4 |
| Chemical Structure |
 |
| CAS Registry Number |
82419-36-1 |
| InChI Identifier |
InChI=1/C18H20FN3O4/c1-10-9-26-17-14-11(16(23)12(18(24)25)8-22(10)14)7-13(19)15(17)21-5-3-20(2)4-6-21/h7-8,10H,3-6,9H2,1-2H3,(H,24,25)/f/h24H |
| InChI Key |
GSDSWSVVBLHKDQ-LQFNOIFHCT |
| KEGG Drug |
D00453  |
| KEGG Compound |
C07321  |
| PubChem Compound |
4583  |
| PubChem Substance |
192373  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA450684  |
| HET ID |
XED  |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02243474  |
| RxList Link |
http://www.rxlist.com/cgi/generic/oflox.htm  |
| PDRhealth Link |
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/flo1181.shtml  |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Ofloxacin  |
| FDA Label |
|
| Material Safety Data Sheet (MSDS) |
|
| Synthesis Reference |
I. Hayakava et al., U.S. Pat. 4,382,892 (1983) |
| Average Molecular Weight |
361.3675 |
| Monoisotopic Molecular Weight |
361.1438 |
| State |
Solid |
| Melting Point |
250-257 oC |
| Experimental Water Solubility |
28.3 mg/mL
Source: PhysProp
|
| Predicted Water Solubility |
1.44e+00 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
2.1
Source: PhysProp
|
| Predicted LogP |
-0.02
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-2.40
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
Not Available |
| Isomeric SMILES |
C[C@H]1COC2=C3N1C=C(C(O)=O)C(=O)C3=CC(F)=C2N1CCN(C)CC1 |
| Canonical SMILES |
CC1COC2=C3N1C=C(C(O)=O)C(=O)C3=CC(F)=C2N1CCN(C)CC1 |
| Drug Category |
- Anti-Bacterial Agents
- Anti-Infective Agents, Urinary
- Anti-Infectives
- Nucleic Acid Synthesis Inhibitors
- Quinolones
|
| ATC Codes |
|
| AHFS Codes |
|
| Indication |
For the treatment of infections (respiratory tract, kidney, skin, soft tissue, UTI), urethral and cervical gonorrhoea. |
| Pharmacology |
Ofloxacin is a quinolone/fluoroquinolone antibiotic. Ofloxacin 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. Ofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. |
| Mechanism of Action |
Ofloxacin acts on DNA gyrase, an enzyme which, like human topoisomerase, prevents the excessive supercoiling of DNA during replication or transcription. |
| Absorption |
Bioavailability of ofloxacin in the tablet formulation is approximately 98% |
| Toxicity |
LD50=5450 mg/kg (orally in mice) |
| Protein Binding |
32% |
| Biotransformation |
Hepatic |
| Half Life |
9 hours |
| Dosage Forms |
| Form |
Route |
| Liquid |
Ophthalmic |
| Solution |
Ophthalmic |
| Tablet |
Oral |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
| Drug |
Interaction |
| Acenocoumarol |
The quinolone increases the anticoagulant effect |
| Aluminium |
Formation of non-absorbable complexes |
| Anisindione |
The quinolone increases the anticoagulant effect |
| Bismuth |
Formation of non-absorbable complexes |
| Calcium |
Formation of non-absorbable complexes |
| Dicumarol |
The quinolone increases the anticoagulant effect |
| Dihydroquinidine barbiturate |
Increased risk of cardiotoxicity and arrhythmias |
| Foscarnet |
Increased risk of convulsions |
| Iron |
Formation of non-absorbable complexes |
| Magnesium |
Formation of non-absorbable complexes |
| Magnesium oxide |
Formation of non-absorbable complexes |
| Procainamide |
The quinolone increases the effect of procainamide |
| Quinidine |
Increased risk of cardiotoxicity and arrhythmias |
| Quinidine barbiturate |
Increased risk of cardiotoxicity and arrhythmias |
| Sucralfate |
Formation of non-absorbable complexes |
| Warfarin |
The quinolone increases the anticoagulant effect |
| Zinc |
Formation of non-absorbable complexes |
|
| Food Interactions |
- Avoid high doses of caffeine.
- Take without regard to meals.
|
| Pathways |
Not Available
|
| General References |
- Drugs.com

- Wikipedia

- RxList

- PDRhealth

|
| Organisms Affected |
- Enteric bacteria and other eubacteria
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 1A2 (CYP1A2)
|
| Targets |
- DNA gyrase subunit A
- DNA topoisomerase 4 subunit A
- DNA topoisomerase 2-alpha
|
|
Drug Target 1
[top]
|
| Target 1 ID |
404 |
| Target 1 Name |
DNA gyrase subunit A |
| Target 1 Synonyms |
- 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 |
|
| Target 1 Transmembrane Regions |
|
| Target 1 Essentiality |
Essential |
| Target 1 GenBank ID Protein |
1574722  |
| Target 1 UniProtKB/Swiss-Prot ID |
P43700  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
GYRA_HAEIN  |
| Target 1 PDB ID |
Not Available |
| Target 1 Cellular Location |
|
| 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  |
| Target 1 General References |
- 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
]
|
| Target 1 Drug References |
- 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
]
- Shi R, Zhang J, Li C, Kazumi Y, Sugawara I: Emergence of ofloxacin resistance in Mycobacterium tuberculosis clinical isolates from China as determined by gyrA mutation analysis using denaturing high-pressure liquid chromatography and DNA sequencing. J Clin Microbiol. 2006 Dec;44(12):4566-8. Epub 2006 Oct 11. [PubMed
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
- Cambau E, Sougakoff W, Besson M, Truffot-Pernot C, Grosset J, Jarlier V: Selection of a gyrA mutant of Mycobacterium tuberculosis resistant to fluoroquinolones during treatment with ofloxacin. J Infect Dis. 1994 Nov;170(5):1351. [PubMed
]
- Schmitz FJ, Hofmann B, Hansen B, Scheuring S, Luckefahr M, Klootwijk M, Verhoef J, Fluit A, Heinz HP, Kohrer K, Jones ME: Relationship between ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039) MICs and mutations in grlA, grlB, gyrA and gyrB in 116 unrelated clinical isolates of Staphylococcus aureus. J Antimicrob Chemother. 1998 Apr;41(4):481-4. [PubMed
]
|
|
Drug Target 2
[top]
|
| Target 2 ID |
477 |
| Target 2 Name |
DNA topoisomerase 4 subunit A |
| Target 2 Synonyms |
- EC 5.99.1.-
- 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 |
|
| Target 2 Transmembrane Regions |
|
| Target 2 Essentiality |
Essential |
| Target 2 GenBank ID Protein |
1574370  |
| Target 2 UniProtKB/Swiss-Prot ID |
P43702  |
| Target 2 UniProtKB/Swiss-Prot Entry Name |
PARC_HAEIN  |
| 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  |
| Target 2 General References |
- 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
]
|
| Target 2 Drug References |
- Turner AK, Nair S, Wain J: The acquisition of full fluoroquinolone resistance in Salmonella Typhi by accumulation of point mutations in the topoisomerase targets. J Antimicrob Chemother. 2006 Oct;58(4):733-40. Epub 2006 Aug 8. [PubMed
]
- 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
]
- Ishiguro F, Toho M, Yamazaki M, Matsuyuki S, Moriya K, Tanaka D, Isobe J, Kyota Y, Muraoka M: [Mutations of gyrA gene and parC gene in fluoroquinolone-resistant Escherichia coli isolates from sporadic diarrheal cases] Kansenshogaku Zasshi. 2006 Sep;80(5):507-12. [PubMed
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
- Chau TT, Campbell JI, Galindo CM, Van Minh Hoang N, Diep TS, Nga TT, Van Vinh Chau N, Tuan PQ, Page AL, Ochiai RL, Schultsz C, Wain J, Bhutta ZA, Parry CM, Bhattacharya SK, Dutta S, Agtini M, Dong B, Honghui Y, Anh DD, Canh DG, Naheed A, Albert MJ, Phetsouvanh R, Newton PN, Basnyat B, Arjyal A, La TT, Rang NN, Phuong LT, Van Be Bay P, von Seidlein L, Dougan G, Clemens JD, Vinh H, Hien TT, Chinh NT, Acosta CJ, Farrar J, Dolecek C: Salmonella enterica Serovar Typhi: Antimicrobial drug resistance in Asia and the molecular mechanism of reduced susceptibility to the fluoroquinolones. Antimicrob Agents Chemother. 2007 Oct 1;. [PubMed
]
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Drug Target 3
[top]
|
| Target 3 ID |
817 |
| Target 3 Name |
DNA topoisomerase 2-alpha |
| Target 3 Synonyms |
- DNA topoisomerase II, alpha isozyme
- 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 |
|
| Target 3 Transmembrane Regions |
|
| Target 3 Essentiality |
Non-Essential |
| Target 3 GenBank ID Protein |
292830  |
| Target 3 UniProtKB/Swiss-Prot ID |
P11388  |
| Target 3 UniProtKB/Swiss-Prot Entry Name |
TOP2A_HUMAN  |
| 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  |
| Target 3 GenAtlas ID |
TOP2A  |
| Target 3 HGNC ID |
HGNC:11989  |
| Target 3 Chromosome Location |
17 |
| Target 3 Locus |
17q21-q22 |
| Target 3 SNPs |
SNPJam Report  |
| Target 3 General References |
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
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| Target 3 Drug References |
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed
]
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