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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:36
Primary Accession Number DB01030
Secondary Accession Number
  • APRD00687
Name Topotecan
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerases, type I. [PubChem]
Synonyms
  1. TPT
  2. TTC
  3. Topotecan Hcl
  4. Topotecan Hydrochloride
  5. Topotecan Lactone
  6. Topotecane [INN-French]
  7. Topotecanum [INN-Latin]
  8. topotecan
Brand Names
  1. Hycamptamine
  2. Hycamptin
  3. Hycamtin
Brand Mixtures Not Available
Chemical IUPAC Name (S)-10-[(dimethylamino) methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3', 4']
Chemical Formula C23H23N3O5
Chemical Structure Structure
CAS Registry Number 119413-54-6
InChI Identifier InChI=1/C23H23N3O5/c1-4-23(30)16-8-18-20-12(9-26(18)21(28)15(16)11-31-22(23)29)7-13-14(10-25(2)3)19(27)6-5-17(13)24-20/h5-8,27,30H,4,9-11H2,1-3H3/t23-/m0/s1
InChI Key UCFGDBYHRUNTLO-QHCPKHFHBX
KEGG Drug Not Available
KEGG Compound C11158 Link Image
PubChem Compound 60700 Link Image
PubChem Substance 606579 Link Image
ChEBI ID Not Available
PharmGKB ID PA451729 Link Image
HET ID TTC Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02231116 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/topotec.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Topotecan Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 421.4458
Monoisotopic Molecular Weight 421.1638
State Solid
Melting Point 213-218 oC
Experimental Water Solubility 1 mg/ml Source: PhysProp
Predicted Water Solubility 8.61e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 0.8 Source: PhysProp
Predicted LogP 1.84 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.69 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@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=C(C=CC(O)=C4CN(C)C)N=C13)C2=O
Canonical SMILES CCC1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=C(C=CC(O)=C4CN(C)C)N=C13)C2=O
Drug Category
  • Antineoplastic Agents
  • Enzyme Inhibitors
ATC Codes
AHFS Codes
  • 10:00.00
Indication For the treatment of metastatic carcinoma of the ovary and small cell lung cancer following the failure of first-line chemotherapy.
Pharmacology Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the Camptotheca acuminata tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells may also be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug.
Mechanism of Action Topotecan has the same mechanism of action as irinotecan. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. The cytotoxicity of topotecan is thought to be due to double strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topotecan, topoisomerase I and DNA. Mammalian cells cannot efficiently repair these double strand breaks.
Absorption Not Available
Toxicity The primary anticipated complication of overdosage would consist of bone marrow suppression.
Protein Binding 35%
Biotransformation Topotecan undergoes a reversible pH dependent hydrolysis of its lactone moiety; it is the lactone form that is pharmacologically active.
Half Life 2-3 hours
Dosage Forms
Form Route
Powder, for solution Intravenous
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Amiodarone The p-glycoprotein inhibitor, Amiodarone, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Atorvastatin The p-glycoprotein inhibitor, Atorvastatin, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Carboplatin Administration of Topotecan after Carboplatin therapy may increase the risk of hematologic toxicity, such as neutropenia and/or thrombocytopenia. A dose adjustment may be required or the sequence of administration reversed.
Carvedilol The p-glycoprotein inhibitor, Carvedilol, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Cisplatin Administration of Topotecan after Cisplatin therapy may increase the risk of hematologic toxicity, such as neutropenia and/or thrombocytopenia. A dose adjustment may be required or the sequence of administration reversed.
Clarithromycin The p-glycoprotein inhibitor, Clarithromycin, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Cyclosporine The p-glycoprotein inhibitor, Cyclosporine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Darunavir The p-glycoprotein inhibitor, Darunavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Dipyridamole The p-glycoprotein inhibitor, Dipyridamole, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Erythromycin The p-glycoprotein inhibitor, Erythromycin, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Filgrastim Filgrastim may increase the adverse effects of Topotecan. Increased risk of prolonged neutropenia. Filgrastim should be administered at least 24 hours following Topotecan therapy. Monitor for signs and symptoms of neutropenia.
Gefitinib The BCRP/ABCG2 inhibitor, Gefitnib, may increase the bioavailability and serum concentration of oral Topotecan. Monitor for change in the therapeutic and adverse effects of Topotecan if Gefitinib is initiated, discontinued or dose changed.
Imatinib The BCRP/ABCG2 inhibitor, Imatinib, may increase the bioavailability and serum concentration of oral Topotecan. Monitor for change in the therapeutic and adverse effects of Topotecan if Imatinib is initiated, discontinued or dose changed.
Itraconazole The p-glycoprotein inhibitor, Itraconazole, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Ketoconazole The p-glycoprotein inhibitor, Ketoconazole, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Lapatinib The p-glycoprotein inhibitor, Lapatinib, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Lopinavir The p-glycoprotein inhibitor, Lopinavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Mefloquine The p-glycoprotein inhibitor, Mefloquine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Natalizumab The immunosuppressant, Topotecan, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
Nelfinavir The p-glycoprotein inhibitor, Nelfinavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Nicardipine The p-glycoprotein inhibitor, Nicardipine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Nilotinib The p-glycoprotein inhibitor, Nilotinib, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Oxaliplatin Administration of Topotecan after Oxaliplatin therapy may increase the risk of hematologic toxicity, such as neutropenia and/or thrombocytopenia. A dose adjustment may be required or the sequence of administration reversed.
Pantoprazole The BCRP/ABCG2 inhibitor, Pantaprazole, may increase the bioavailability and serum concentration of oral Topotecan. Monitor for change in the therapeutic and adverse effects of Topotecan if Pantaprazole is initiated, discontinued or dose changed.
Progesterone The p-glycoprotein inhibitor, Progesterone, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Propranolol The p-glycoprotein inhibitor, Propranolol, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Quinidine The p-glycoprotein inhibitor, Quinidine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Ranolazine The p-glycoprotein inhibitor, Ranolazine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Reserpine The p-glycoprotein inhibitor, Reserpine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Ritonavir The p-glycoprotein inhibitor, Ritonavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Saquinavir The p-glycoprotein inhibitor, Saquinavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Sunitinib The p-glycoprotein inhibitor, Sunitinib, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Tacrolimus The p-glycoprotein inhibitor, Tacrolimus, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Tamoxifen The p-glycoprotein inhibitor, Tamoxifen, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Verapamil The p-glycoprotein inhibitor, Verapamil, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
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. DNA topoisomerase I, mitochondrial
  2. DNA topoisomerase 1
  3. ATP-binding cassette sub-family G member 2
Drug Target 1 [top]
Target 1 ID 102
Target 1 Name DNA topoisomerase I, mitochondrial
Target 1 Synonyms
  1. DNA topoisomerase I, mitochondrial precursor
  2. EC 5.99.1.2
  3. TOP1mt
Target 1 Gene Name TOP1MT
Target 1 Protein Sequence >DNA topoisomerase I, mitochondrial precursor 
MRVVRLLRLRAALTLLGEVPRRPASRGVPGSRRTQKGSGARWEKEKHEDGVKWRQLEHKG
PYFAPPYEPLPDGVRFFYEGRPVRLSVAAEEVATFYGRMLDHEYTTKEVFRKNFFNDWRK
EMAVEEREVIKSLDKCDFTEIHRYFVDKAAARKVLSREEKQKLKEEAEKLQQEFGYCILD
GHQEKIGNFKIEPPGLFRGRGDHPKMGMLKRRITPEDVVINCSRDSKIPEPPAGHQWKEV
RSDNTVTWLAAWTESVQNSIKYIMLNPCSKLKGETAWQKFETARRLRGFVDEIRSQYRAD
WKSREMKTRQRAVALYFIDKLALRAGNEKEDGEAADTVGCCSLRVEHVQLHPEADGCQHV
VEFDFLGKDCIRYYNRVPVEKPVYKNLQLFMENKDPRDDLFDRLTTTSLNKHLQELMDGL
TAKVFRTYNASITLQEQLRALTRAEDSIAAKILSYNRANRVVAILCNHQRATPSTFEKSM
QNLQTKIQAKKEQVAEARAELRRARAEHKAQGDGKSRSVLEKKRRLLEKLQEQLAQLSVQ
ATDKEENKQVALGTSKLNYLDPRISIAWCKRFRVPVEKIYSKTQRERFAWALAMAGEDFE
F
Target 1 Number of Residues 611
Target 1 Molecular Weight 69873
Target 1 Theoretical pI 9.94
Target 1 GO Classification
Function
DNA topoisomerase activity
DNA topoisomerase type I 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
Not Available
Target 1 General Function Replication, recombination and repair
Target 1 Specific Function Relieves DNA strain that arise during duplication of mitochondrial DNA
Target 1 Pathways Not Available
Target 1 Reactions
  • ATP-independent breakage of single-stranded DNA, followed by passage and rejoining INHIBITOR Camptothecin
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 15919359 Link Image
Target 1 UniProtKB/Swiss-Prot ID Q969P6 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name TOP1M_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Mitochondrion
Target 1 Gene Sequence >1806 bp 
ATGCGCGTGGTGCGGCTGCTGCGGCTCCGGGCGGCTCTGACGCTGCTCGGGGAGGTCCCC
CGCCGCCCGGCCTCCCGGGGTGTCCCGGGCTCGCGCAGGACGCAGAAGGGCAGTGGAGCC
AGGTGGGAGAAGGAGAAGCACGAAGACGGGGTGAAGTGGAGACAGCTGGAGCACAAGGGC
CCGTACTTCGCACCCCCATACGAGCCCCTTCCCGACGGAGTGCGTTTCTTCTATGAAGGA
AGGCCTGTGAGATTGAGCGTGGCAGCGGAGGAGGTCGCCACTTTTTATGGGAGGATGTTA
GATCATGAATACACAACAAAGGAGGTTTTCCGGAAGAACTTCTTCAATGACTGGCGAAAG
GAAATGGCGGTGGAAGAGAGGGAAGTCATCAAGAGCCTGGACAAGTGTGACTTCACGGAG
ATCCACAGATACTTTGTGGACAAGGCCGCAGCCCGGAAAGTCCTGAGCAGGGAGGAGAAG
CAGAAGCTAAAAGAAGAGGCAGAAAAACTTCAGCAAGAGTTCGGCTACTGTATTTTAGAT
GGTCACCAAGAAAAAATAGGCAACTTCAAGATTGAGCCGCCTGGCTTGTTCCGTGGCCGT
GGCGACCATCCCAAGATGGGGATGCTGAAGAGAAGGATCACGCCAGAGGATGTGGTTATC
AACTGCAGCAGGGACTCGAAGATCCCCGAGCCGCCGGCGGGGCACCAGTGGAAGGAGGTG
CGCTCCGATAACACCGTCACGTGGCTGGCAGCTTGGACCGAGAGCGTTCAGAACTCCATC
AAGTACATCATGCTGAACCCTTGCTCGAAGCTGAAGGGGGAGACAGCTTGGCAGAAGTTT
GAAACAGCTCGACGCCTGCGGGGATTTGTGGACGAGATCCGCTCCCAGTACCGGGCTGAC
TGGAAGTCTCGGGAAATGAAGACGAGACAGCGGGCGGTGGCCCTGTATTTCATCGATAAG
CTGGCACTGAGAGCAGGAAATGAGAAGGAGGACGGTGAGGCGGCCGACACCGTGGGCTGC
TGTTCCCTCCGCGTGGAGCACGTCCAGCTGCACCCGGAGGCCGATGGCTGCCAACACGTG
GTGGAATTTGACTTCCTGGGGAAGGACTGCATCCGCTACTACAACAGAGTGCCGGTGGAG
AAGCCGGTGTACAAGAACTTACAGCTCTTTATGGAGAACAAGGACCCCCGGGACGACCTC
TTCGACAGGCTGACCACGACCAGCCTGAACAAGCACCTCCAGGAGCTGATGGACGGGCTG
ACGGCCAAGGTGTTCCGGACCTACAACGCCTCCATCACTCTGCAGGAGCAGCTGCGGGCC
CTGACGCGCGCCGAGGACAGCATAGCAGCTAAGATCTTATCCTACAACCGAGCCAACCGA
GTCGTGGCCATTCTCTGCAACCATCAGCGAGCAACCCCCAGTACGTTCGAGAAGTCGATG
CAGAATCTCCAGACGAAGATCCAGGCAAAGAAGGAGCAGGTGGCTGAGGCCAGGGCAGAG
CTGAGGAGGGCGAGGGCTGAGCACAAAGCCCAAGGGGATGGCAAGTCCAGGAGTGTCCTG
GAGAAGAAGAGGCGGCTCCTGGAGAAGCTGCAGGAGCAGCTGGCGCAGCTGAGTGTGCAG
GCCACGGACAAGGAGGAGAACAAGCAGGTGGCCCTGGGCACGTCCAAGCTCAACTACCTG
GACCCCAGGATCAGCATTGCCTGGTGCAAGCGGTTCAGGGTGCCAGTGGAGAAGATCTAC
AGCAAAACACAGCGGGAGAGGTTCGCCTGGGCTCTCGCCATGGCAGGAGAAGACTTTGAA
TTCTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID TOP1MT Link Image
Target 1 GenAtlas ID TOP1MT Link Image
Target 1 HGNC ID HGNC:29787 Link Image
Target 1 Chromosome Location 8
Target 1 Locus 8q24.3
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Zhang H, Barcelo JM, Lee B, Kohlhagen G, Zimonjic DB, Popescu NC, Pommier Y: Human mitochondrial topoisomerase I. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10608-13. Epub 2001 Aug 28. [PubMed Link Image]
Target 1 Drug References
  1. Kosovsky MJ, Soslau G: Immunological identification of human platelet mitochondrial DNA topoisomerase I. Biochim Biophys Acta. 1993 Jun 24;1164(1):101-7. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 1353
Target 2 Name DNA topoisomerase 1
Target 2 Synonyms
  1. DNA topoisomerase I
  2. EC 5.99.1.2
Target 2 Gene Name TOP1
Target 2 Protein Sequence >DNA topoisomerase 1 
MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKK
HKEKEKTKHKDGSSEKHKDKHKDRDKEKRKEEKVRASGDAKIKKEKENGFSSPPQIKDEP
EDDGYFVPPKEDIKPLKRPRDEDDADYKPKKIKTEDTKKEKKRKLEEEEDGKLKKPKNKD
KDKKVPEPDNKKKKPKKEEEQKWKWWEEERYPEGIKWKFLEHKGPVFAPPYEPLPENVKF
YYDGKVMKLSPKAEEVATFFAKMLDHEYTTKEIFRKNFFKDWRKEMTNEEKNIITNLSKC
DFTQMSQYFKAQTEARKQMSKEEKLKIKEENEKLLKEYGFCIMDNHKERIANFKIEPPGL
FRGRGNHPKMGMLKRRIMPEDIIINCSKDAKVPSPPPGHKWKEVRHDNKVTWLVSWTENI
QGSIKYIMLNPSSRIKGEKDWQKYETARRLKKCVDKIRNQYREDWKSKEMKVRQRAVALY
FIDKLALRAGNEKEEGETADTVGCCSLRVEHINLHPELDGQEYVVEFDFLGKDSIRYYNK
VPVEKRVFKNLQLFMENKQPEDDLFDRLNTGILNKHLQDLMEGLTAKVFRTYNASITLQQ
QLKELTAPDENIPAKILSYNRANRAVAILCNHQRAPPKTFEKSMMNLQTKIDAKKEQLAD
ARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMKLEVQATDREENKQIALGTSK
LNYLDPRITVAWCKKWGVPIEKIYNKTQREKFAWAIDMADEDYEF
Target 2 Number of Residues 777
Target 2 Molecular Weight 90726
Target 2 Theoretical pI 9.95
Target 2 GO Classification
Function
DNA topoisomerase activity
DNA topoisomerase type I 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
Not Available
Target 2 General Function Replication, recombination and repair
Target 2 Specific Function The reaction catalyzed by topoisomerases leads to the conversion of one topological isomer of DNA to another
Target 2 Pathways Not Available
Target 2 Reactions
  • ATP-independent breakage of single-stranded DNA, followed by passage and rejoining INHIBITOR Camptothecin
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 339806 Link Image
Target 2 UniProtKB/Swiss-Prot ID P11387 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name TOP1_HUMAN Link Image
Target 2 PDB ID 1A36 Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Cytoplasmic
Target 2 Gene Sequence >2298 bp 
ATGAGTGGGGACCACCTCCACAACGATTCCCAGATCGAAGCGGATTTCCGATTGAATGAT
TCTCATAAACACAAAGATAAACACAAAGATCGAGAACACCGGCACAAAGAACACAAGAAG
GAGAAGGACCGGGAAAAGTCCAAGCATAGCAACAGTGAACATAAAGATTCTGAAAAGAAA
CACAAAGAGAAGGAGAAGACCAAACACAAAGATGGAAGCTCAGAAAAGCATAAAGACAAA
CATAAAGACAGAGACAAGGAAAAACGAAAAGAGGAAAAGGTTCGAGCCTCTGGGGATGCA
AAAATAAAGAAGGAGAAGGAAAATGGCTTCTCTAGTCCACCACAAATTAAAGATGAACCT
GAAGATGATGGCTATTTTGTTCCTCCTAAAGAGGATATAAAGCCATTAAAGAGACCTCGA
GATGAGGATGATGTTGATTATAAACCTAAGAAAATTAAAACAGAAGATACCAAGAAGGAG
AAGAAAAGAAAACTAGAAGAAGAAGAGGATGGTAAATTGAAAAAACCCAAGAATAAAGAT
AAAGATAAAAAAGTTCCTGAGCCAGATAACAAGAAAAAGAAGCCGAAGAAAGAAGAGGAA
CAGAAGTGGAAATGGTGGGAAGAAGAGCGCTATCCTGAAGGCATCAAGTGGAAATTCCTA
GAACATAAAGGTCCAGTATTTGCCCCACCATATGAGCCTCTTCCAGAGAATGTCAAGTTT
TATTATGATGGTAAAGTCATGAAGCTGAGCCCCAAAGCAGAGGAAGTAGCTACGTTCTTT
GCAAAAATGCTCGACCATGAATATACTACCAAGGAAATATTTAGGAAAAATTTCTTTAAA
GACTGGAGAAAGGAAATGACTAATGAAGAGAAGAATATTATCACCAACCTAAGCAAATGT
GATTTTACCCAGATGAGCCAGTATTTCAAAGCCCAGACGGAAGCTCGGAAACAGATGAGC
AAGGAAGAGAAACTGAAAATCAAAGAGGAGAATGAAAAATTACTGAAAGAATATGGATTC
TGTATTATGGATAACCACAAAGAGAGGATTGCTAACTTCAAGATAGAGCCTCCTGGACTT
TTCCGTGGCCGCGGCAACCACCCCAAGATGGGCATGCTGAAGAGACGAATCATGCCCGAG
GATATAATCATCAACTGTAGCAAAGATGCCAAGGTTCCTTCTCCTCCTCCAGGACATAAG
TGGAAAGAAGTCCGGCATGATAACAAGGTTACTTGGCTGGTTTCCTGGACAGAGAACATC
CAAGGTTCCATTAAATACATCATGCTTAACCCTAGTTCACGAATCAAGGGTGAGAAGGAC
TGGCAGAAATACGAGACTGCTCGGCGGCTGAAAAAATGTGTGGACAAGATCCGGAACCAG
TATCGAGAAGACTGGAAGTCCAAAGAGATGAAAGTCCGGCAGAGAGCTGTAGCCCTGTAC
TTCATCGACAAGCTTGCTCTGAGAGCAGGCAATGAAAAGGAGGAAGGAGAAACAGCGGAC
ACTGTGGGCTGCTGCTCACTTCGTGTGGAGCACATCAATCTACACCCAGAGTTGGATGGT
CAGGAATATGTGGTAGAGTTTGACTTCCTCGGGAAGGACTCCATCAGATACTATAACAAG
GTCCCTGTTGAGAAACGAGTTTTTAAGAACCTACAACTATTTATGGAGAACAAGCAGCCC
GAGGATGATCTTTTTGATAGACTCAATACTGGTATTCTGAATAAGCATCTTCAGGATCTC
ATGGAGGGCTTGACAGCCAAGGTATTCCGTACGTACAATGCCTCCATCACGCTACAGCAG
CAGCTAAAAGAACTGACAGCCCCGGATGAGAACATCCCAGCGAAGATCCTTTCTTATAAC
CGTGCCAATCGAGCTGTTGCAATTCTTTGTAACCATCAGAGGGCACCACCAAAAACTTTT
GAGAAGTCTATGATGAACTTGCAAACTAAGATTGATGCCAAGAAGGAACAGCTAGCAGAT
GCCCGGAGAGACCTGAAAAGTGCTAAGGCTGATGCCAAGGTCATGAAGGATGCAAAGACG
AAGAAGGTAGTAGAGTCAAAGAAGAAGGCTGTTCAGAGACTGGAGGAACAGTTGATGAAG
CTGGAAGTTCAAGCCACAGACCGAGAGGAAAATAAACAGATTGCCCTGGGAACCTCCAAA
CTCAATTATCTGGACCCTAGGATCACAGTGGCTTGGTGCAAGAAGTGGGGTGTCCCAATT
GAGAAGATTTACAACAAAACCCAGCGGGAGAAGTTTGCCTGGGCCATTGACATGGCTGAT
GAAGACTATGAGTTTTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID TOP1 Link Image
Target 2 GenAtlas ID TOP1 Link Image
Target 2 HGNC ID HGNC:11986 Link Image
Target 2 Chromosome Location 20
Target 2 Locus 20q12-q13.1
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Ahuja HG, Felix CA, Aplan PD: The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion. Blood. 1999 Nov 1;94(9):3258-61. [PubMed Link Image]
  2. Redinbo MR, Champoux JJ, Hol WG: Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA. Biochemistry. 2000 Jun 13;39(23):6832-40. [PubMed Link Image]
  3. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [PubMed Link Image]
  4. Kubota N, Kanzawa F, Nishio K, Takeda Y, Ohmori T, Fujiwara Y, Terashima Y, Saijo N: Detection of topoisomerase I gene point mutation in CPT-11 resistant lung cancer cell line. Biochem Biophys Res Commun. 1992 Oct 30;188(2):571-7. [PubMed Link Image]
  5. Tamura H, Kohchi C, Yamada R, Ikeda T, Koiwai O, Patterson E, Keene JD, Okada K, Kjeldsen E, Nishikawa K, et al.: Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites. Nucleic Acids Res. 1991 Jan 11;19(1):69-75. [PubMed Link Image]
  6. Kunze N, Yang GC, Dolberg M, Sundarp R, Knippers R, Richter A: Structure of the human type I DNA topoisomerase gene. J Biol Chem. 1991 May 25;266(15):9610-6. [PubMed Link Image]
  7. Kunze N, Klein M, Richter A, Knippers R: Structural characterization of the human DNA topoisomerase I gene promoter. Eur J Biochem. 1990 Dec 12;194(2):323-30. [PubMed Link Image]
  8. Oddou P, Schmidt U, Knippers R, Richter A: Monoclonal antibodies neutralizing mammalian DNA topoisomerase I activity. Eur J Biochem. 1988 Nov 15;177(3):523-9. [PubMed Link Image]
  9. Maul GG, Jimenez SA, Riggs E, Ziemnicka-Kotula D: Determination of an epitope of the diffuse systemic sclerosis marker antigen DNA topoisomerase I: sequence similarity with retroviral p30gag protein suggests a possible cause for autoimmunity in systemic sclerosis. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8492-6. [PubMed Link Image]
  10. Zhou BS, Bastow KF, Cheng YC: Characterization of the 3' region of the human DNA topoisomerase I gene. Cancer Res. 1989 Jul 15;49(14):3922-7. [PubMed Link Image]
  11. 2833744 D'Arpa P, Machlin PS, Ratrie H 3rd, Rothfield NF, Cleveland DW, Earnshaw WC: cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2543-7.
  12. 7882333 Fujimori A, Harker WG, Kohlhagen G, Hoki Y, Pommier Y: Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin. Cancer Res. 1995 Mar 15;55(6):1339-46.
  13. 9488644 Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG: Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Science. 1998 Mar 6;279(5356):1504-13.
  14. 9488652 Stewart L, Redinbo MR, Qiu X, Hol WG, Champoux JJ: A model for the mechanism of human topoisomerase I. Science. 1998 Mar 6;279(5356):1534-41.
Target 2 Drug References
  1. Schmidt F, Rieger J, Wischhusen J, Naumann U, Weller M: Glioma cell sensitivity to topotecan: the role of p53 and topotecan-induced DNA damage. Eur J Pharmacol. 2001 Jan 19;412(1):21-5. [PubMed Link Image]
  2. strel'tsov SA, Mikheikin AL, Nechipurenko IuD: [Interaction of topotecan--a DNA topoisomerase I inhibitor--with dual-stranded polydeoxyribonucleotides. II. Formation of a complex containing several DNA molecules in the presence of topotecan] Mol Biol (Mosk). 2001 May-Jun;35(3):442-50. [PubMed Link Image]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  4. Streltsov SA: Action models for the antitumor drug camptothecin: formation of alkali-labile complex with DNA and inhibition of human DNA topoisomerase I. J Biomol Struct Dyn. 2002 Dec;20(3):447-54. [PubMed Link Image]
  5. Zhang J, Pu SP, Zhou YJ: [Preliminary study of apoptosis of human hepatocarcinoma cell line HepG2 induced by topotecan] Ai Zheng. 2002 Dec;21(12):1305-9. [PubMed Link Image]
  6. Aisner J, Musanti R, Beers S, Smith S, Locsin S, Rubin EH: Sequencing topotecan and etoposide plus cisplatin to overcome topoisomerase I and II resistance: a pharmacodynamically based Phase I trial. Clin Cancer Res. 2003 Jul;9(7):2504-9. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 1732
Target 3 Name ATP-binding cassette sub-family G member 2
Target 3 Synonyms
  1. Breast cancer resistance protein
  2. CD338 antigen
  3. CDw338
  4. Mitoxantrone resistance-associated protein
  5. Placenta-specific ATP- binding cassette transporter
Target 3 Gene Name ABCG2
Target 3 Protein Sequence >ATP-binding cassette sub-family G member 2 
MSSSNVEVFIPVSQGNTNGFPATASNDLKAFTEGAVLSFHNICYRVKLKSGFLPCRKPVE
KEILSNINGIMKPGLNAILGPTGGGKSSLLDVLAARKDPSGLSGDVLINGAPRPANFKCN
SGYVVQDDVVMGTLTVRENLQFSAALRLATTMTNHEKNERINRVIQELGLDKVADSKVGT
QFIRGVSGGERKRTSIGMELITDPSILFLDEPTTGLDSSTANAVLLLLKRMSKQGRTIIF
SIHQPRYSIFKLFDSLTLLASGRLMFHGPAQEALGYFESAGYHCEAYNNPADFFLDIING
DSTAVALNREEDFKATEIIEPSKQDKPLIEKLAEIYVNSSFYKETKAELHQLSGGEKKKK
ITVFKEISYTTSFCHQLRWVSKRSFKNLLGNPQASIAQIIVTVVLGLVIGAIYFGLKNDS
TGIQNRAGVLFFLTTNQCFSSVSAVELFVVEKKLFIHEYISGYYRVSSYFLGKLLSDLLP
MRMLPSIIFTCIVYFMLGLKPKADAFFVMMFTLMMVAYSASSMALAIAAGQSVVSVATLL
MTICFVFMMIFSGLLVNLTTIASWLSWLQYFSIPRYGFTALQHNEFLGQNFCPGLNATGN
NPCNYATCTGEEYLVKQGIDLSPWGLWKNHVALACMIVIFLTIAYLKLLFLKKYS
Target 3 Number of Residues 665
Target 3 Molecular Weight 72315
Target 3 Theoretical pI 8.90
Target 3 GO Classification
Function
ATPase activity
purine nucleotide binding
adenyl nucleotide binding
ATP binding
catalytic activity
hydrolase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
nucleoside-triphosphatase activity
binding
nucleotide binding
Process
Not Available
Component
Not Available
Target 3 General Function Defense mechanisms and xenobiotic export
Target 3 Specific Function Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 396-416
  • 429-449
  • 478-498
  • 507-527
  • 536-556
  • 631-651
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 4185796 Link Image
Target 3 UniProtKB/Swiss-Prot ID Q9UNQ0 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name ABCG2_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Cell membrane
  • multi-pass membrane protein
Target 3 Gene Sequence >1968 bp 
ATGTCTTCCAGTAATGTCGAAGTTTTTATCCCAGTGTCACAAGGAAACACCAATGGCTTC
CCCGCGACAGTTTCCAATGACCTGAAGGCATTTACTGAAGGAGCTGTGTTAAGTTTTCAT
AACATCTGCTATCGAGTAAAACTGAAGAGTGGCTTTCTACCTTGTCGAAAACCAGTTGAG
AAAGAAATATTATCGAATATCAATGGGATCATGAAACCTGGTCTCAACGCCATCCTGGGA
CCCACAGGTGGAGGCAAATCTTCGTTATTAGATGTCTTAGCTGCAAGGAAAGATCCAAGT
GGATTATCTGGAGATGTTCTGATAAATGGAGCACCGCGACCTGCCAATTTCAAATGTAAT
TCAGGTTACGTGGTACAAGATGATGTTGTGATGGGCACTCTGACGGTGAGAGAAAACTTA
CAGTTCTCAGCAGCTCTTCGGCTTGCAACAACTATGACGAATCATGAAAAAAACGAACGG
ATTAACAGGGTCATTGAAGAGTTAGGTCTGGATAAAGTGGCAGACTCCAAGGTTGGAACT
CAGTTTATCCGTGGTGTGTCTGGAGGAGAAAGAAAAAGGACTAGTATAGGAATGGAGCTT
ATCACTGATCCTTCCATCTTGTCCTTGGATGAGCCTACAACTGGCTTAGACTCAAGCACA
GCAAATGCTGTCCTTTTGCTCCTGAAAAGGATGTCTAAGCAGGGACGAACAATCATCTTC
TCCATTCATCAGCCTCGATATTCCATCTTCAAGTTGTTTGATAGCCTCACCTTATTGGCC
TCAGGAAGACTTATGTTCCACGGGCCTGCTCAGGAGGCCTTGGGATACTTTGAATCAGCT
GGTTATCACTGTGAGGCCTATAATAACCCTGCAGACTTCTTCTTGGACATCATTAATGGA
GATTCCACTGCTGTGGCATTAAACAGAGAAGAAGACTTTAAAGCCACAGAGATCATAGAG
CCTTCCAAGCAGGATAAGCCACTCATAGAAAAATTAGCGGAGATTTATGTCAACTCCTCC
TTCTACAAAGAGACAAAAGCTGAATTACATCAACTTTCCGGGGGTGAGAAGAAGAAGAAG
ATCACAGTCTTCAAGGAGATCAGCTACACCACCTCCTTCTGTCATCAACTCAGATGGGTT
TCCAAGCGTTCATTCAAAAACTTGCTGGGTAATCCCCAGGCCTCTATAGCTCAGATCATT
GTCACAGTCGTACTGGGACTGGTTATAGGTGCCATTTACTTTGGGCTAAAAAATGATTCT
ACTGGAATCCAGAACAGAGCTGGGGTTCTCTTCTTCCTGACGACCAACCAGTGTTTCAGC
AGTGTTTCAGCCGTGGAACTCTTTGTGGTAGAGAAGAAGCTCTTCATACATGAATACATC
AGCGGATACTACAGAGTGTCATCTTATTTCCTTGGAAAACTGTTATCTGATTTATTACCC
ATGAGGATGTTACCAAGTATTATATTTACCTGTATAGTGTACTTCATGTTAGGATTGAAG
CCAAAGGCAGATGCCTTCTTCGTTATGATGTTTACCCTTATGATGGTGGCTTATTCAGCC
AGTTCCATGGCACTGGCCATAGCAGCAGGTCAGAGTGTGGTTTCTGTAGCAACACTTCTC
ATGACCATCTGTTTTGTGTTTATGATGATTTTTTCAGGTCTGTTGGTCAATCTCACAACC
ATTGCATCTTGGCTGTCATGGCTTCAGTACTTCAGCATTCCACGATATGGATTTACGGCT
TTGCAGCATAATGAATTTTTGGGACAAAACTTCTGCCCAGGACTCAATGCAACAGGAAAC
AATCCTTGTAACTATGCAACATGTACTGGCGAAGAATATTTGGTAAAGCAGGGCATCGAT
CTCTCACCCTGGGGCTTGTGGAAGAATCACGTGGCCTTGGCTTGTATGATTGTTATTTTC
CTCACAATTGCCTACCTGAAATTGTTATTTCTTAAAAAATATTCTTAA
Target 3 GenBank Gene ID
Target 3 GeneCard ID ABCG2 Link Image
Target 3 GenAtlas ID ABCG2 Link Image
Target 3 HGNC ID HGNC:74 Link Image
Target 3 Chromosome Location 4
Target 3 Locus 4q22
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Komatani H, Kotani H, Hara Y, Nakagawa R, Matsumoto M, Arakawa H, Nishimura S: Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure. Cancer Res. 2001 Apr 1;61(7):2827-32. [PubMed Link Image]
  2. Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP: The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 2001 Sep;7(9):1028-34. [PubMed Link Image]
  3. Schmitz G, Langmann T, Heimerl S: Role of ABCG1 and other ABCG family members in lipid metabolism. J Lipid Res. 2001 Oct;42(10):1513-20. [PubMed Link Image]
  4. Iida A, Saito S, Sekine A, Mishima C, Kitamura Y, Kondo K, Harigae S, Osawa S, Nakamura Y: Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8. J Hum Genet. 2002;47(6):285-310. [PubMed Link Image]
  5. Zhang W, Mojsilovic-Petrovic J, Andrade MF, Zhang H, Ball M, Stanimirovic DB: The expression and functional characterization of ABCG2 in brain endothelial cells and vessels. FASEB J. 2003 Nov;17(14):2085-7. Epub 2003 Sep 4. [PubMed Link Image]
  6. Allikmets R, Schriml LM, Hutchinson A, Romano-Spica V, Dean M: A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res. 1998 Dec 1;58(23):5337-9. [PubMed Link Image]
  7. Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD: A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15665-70. [PubMed Link Image]
Target 3 Drug References
  1. Maliepaard M, van Gastelen MA, de Jong LA, Pluim D, van Waardenburg RC, Ruevekamp-Helmers MC, Floot BG, Schellens JH: Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res. 1999 Sep 15;59(18):4559-63. [PubMed Link Image]
  2. Rocchi E, Khodjakov A, Volk EL, Yang CH, Litman T, Bates SE, Schneider E: The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane. Biochem Biophys Res Commun. 2000 Apr 29;271(1):42-6. [PubMed Link Image]
  3. Ishii M, Iwahana M, Mitsui I, Minami M, Imagawa S, Tohgo A, Ejima A: Growth inhibitory effect of a new camptothecin analog, DX-8951f, on various drug-resistant sublines including BCRP-mediated camptothecin derivative-resistant variants derived from the human lung cancer cell line PC-6. Anticancer Drugs. 2000 Jun;11(5):353-62. [PubMed Link Image]
  4. Yang CH, Schneider E, Kuo ML, Volk EL, Rocchi E, Chen YC: BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells. Biochem Pharmacol. 2000 Sep 15;60(6):831-7. [PubMed Link Image]
  5. Jonker JW, Smit JW, Brinkhuis RF, Maliepaard M, Beijnen JH, Schellens JH, Schinkel AH: Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst. 2000 Oct 18;92(20):1651-6. [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.