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Identification
NameTopotecan
Accession NumberDB01030  (APRD00687)
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionAn antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerases, type I. [PubChem]
Structure
Thumb
Synonyms
9-[(dimethylamino)Methyl]-10-hydroxy-(4S)-camptothecin
Topotecane
Topotecanum
External Identifiers
  • SKF-104864
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act TopotecanPowder, for solution4 mgIntravenousActavis Pharma Company2015-11-17Not applicableCanada
Act TopotecanPowder, for solution1 mgIntravenousActavis Pharma CompanyNot applicableNot applicableCanada
HycamtinInjection, powder, for solution1 mgIntravenousNovartis Europharm Limited1996-11-12Not applicableEu
HycamtinInjection, powder, lyophilized, for solution4 mg/4mLIntravenousGlaxo Smith Kline Llc1996-06-07Not applicableUs
HycamtinPowder, for solution4 mgIntravenousNovartis Pharmaceuticals Canada Inc1997-06-18Not applicableCanada
HycamtinInjection, powder, for solution1 mgIntravenousNovartis Europharm Limited1996-11-12Not applicableEu
HycamtinCapsule.25 mg/1OralGlaxo Smith Kline Llc2008-09-16Not applicableUs
HycamtinInjection, powder, for solution4 mgIntravenousNovartis Europharm Limited1996-11-12Not applicableEu
HycamtinCapsule0.25 mgOralNovartis Europharm Limited1996-11-12Not applicableEu
HycamtinCapsule1 mg/1OralGlaxo Smith Kline Llc2008-09-16Not applicableUs
HycamtinInjection, powder, for solution4 mgIntravenousNovartis Europharm Limited1996-11-12Not applicableEu
HycamtinCapsule1 mgOralNovartis Europharm Limited1996-11-12Not applicableEu
Mylan-topotecan Hydrochloride for InjectionPowder, for solution4 mgIntravenousMylan Pharmaceuticals UlcNot applicableNot applicableCanada
PMS-topotecanPowder, for solution1 mgIntravenousPharmascience IncNot applicableNot applicableCanada
PMS-topotecanPowder, for solution4 mgIntravenousPharmascience Inc2013-08-29Not applicableCanada
TopotecanInjection, solution, concentrate1 mg/mLIntravenousHospira, Inc.2011-02-02Not applicableUs
TopotecanInjection, solution, concentrate1 mg/mLIntravenousSagent Pharmaceuticals2014-12-15Not applicableUs
TopotecanInjection, solution, concentrate1 mg/mLIntravenousTeva Parenteral Medicines, Inc.2013-05-21Not applicableUs
TopotecanInjection1 mg/mLIntravenousSandoz Inc2011-02-25Not applicableUs
Topotecan for InjectionPowder, for solution4 mgIntravenousSandoz Canada Incorporated2009-10-02Not applicableCanada
Topotecan for InjectionPowder, for solution4 mgIntravenousFresenius Kabi Canada Ltd2012-03-16Not applicableCanada
Topotecan HospiraInjection, solution, concentrate4 mg/4mlIntravenousHospira Uk Ltd  2010-06-10Not applicableEu
Topotecan HospiraInjection, solution, concentrate4 mg/4mlIntravenousHospira Uk Ltd  2010-06-10Not applicableEu
Topotecan Hydrochloride for InjectionSolution1 mgIntravenousHospira Healthcare Corporation2012-03-27Not applicableCanada
Topotecan Hydrochloride for InjectionPowder, for solution4 mgIntravenousMylan Pharmaceuticals Ulc2013-06-112016-07-06Canada
Topotecan Hydrochloride for InjectionPowder, for solution4 mgIntravenousAccord Healthcare Inc2011-06-27Not applicableCanada
Topotecan Hydrochloride for InjectionSolution1 mgIntravenousAccord Healthcare Inc2013-11-21Not applicableCanada
Topotecan InjectionSolution1 mgIntravenousTeva Canada Limited2013-10-21Not applicableCanada
Topotecan InjectionSolution1 mgIntravenousSandoz Canada Incorporated2014-02-05Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PotactasolInjection, powder, for solution4 mgIntravenousActavis Group Ptc Ehf2011-01-06Not applicableEu
PotactasolInjection, powder, for solution1 mgIntravenousActavis Group Ptc Ehf2011-01-06Not applicableEu
TopotecanInjection, powder, lyophilized, for solution4 mg/4mLIntravenousIngenus Pharmaceuticals, LLC2016-12-07Not applicableUs
Topotecan ActavisInjection, powder, for solution4 mgIntravenousActavis Group Ptc Ehf2009-07-24Not applicableEu
Topotecan ActavisInjection, powder, for solution1 mgIntravenousActavis Group Ptc Ehf2009-07-24Not applicableEu
Topotecan ActavisInjection, powder, for solution4 mgIntravenousActavis Group Ptc Ehf2009-07-24Not applicableEu
Topotecan ActavisInjection, powder, for solution1 mgIntravenousActavis Group Ptc Ehf2009-07-24Not applicableEu
Topotecan HydrochlorideInjection, powder, for solution4 mg/4mLIntravenousThree Rivers Pharmaceuticals, LLC.2010-12-02Not applicableUs
Topotecan HydrochlorideInjection, powder, lyophilized, for solution4 mg/4mLIntravenousPfizer Laboratories Div Pfizer Inc.2012-08-29Not applicableUs
Topotecan HydrochlorideInjection, powder, lyophilized, for solution4 mg/4mLIntravenousActavis Pharma, Inc.2015-01-05Not applicableUs
Topotecan HydrochlorideInjection, powder, lyophilized, for solution4 mg/mLIntravenousMylan Institutional LLC2012-08-29Not applicableUs
Topotecan HydrochlorideInjection, powder, lyophilized, for solution4 mg/4mLIntravenousAccord Healthcare, Inc.2013-07-01Not applicableUs
Topotecan HydrochlorideInjection, powder, lyophilized, for solution4 mg/4mLIntravenousBedford Laboratories2011-04-18Not applicableUs
Topotecan HydrochlorideInjection, powder, lyophilized, for solution4 mg/4mLIntravenousFresenius Kabi USA, LLC2010-11-29Not applicableUs
Topotecan HydrochlorideInjection, powder, lyophilized, for solution4 mg/4mLIntravenousSagent Pharmaceuticals2010-11-28Not applicableUs
Topotecan HydrochlorideInjection, powder, lyophilized, for solution4 mg/4mLIntravenousSun Pharmaceutical Industries Limited2015-09-02Not applicableUs
Topotecan HydrochlorideInjection, powder, lyophilized, for solution4 mg/4mLIntravenousSagent Pharmaceuticals2011-06-27Not applicableUs
Topotecan TevaInjection, solution, concentrate4 mg/4mlIntravenousTeva B.V.2009-09-21Not applicableEu
Topotecan TevaInjection, solution, concentrate1 mg/1mlIntravenousTeva B.V.2009-09-21Not applicableEu
Topotecan TevaInjection, solution, concentrate1 mg/1mlIntravenousTeva B.V.2009-09-21Not applicableEu
Topotecan TevaInjection, solution, concentrate4 mg/4mlIntravenousTeva B.V.2009-09-21Not applicableEu
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Topotecan hydrochloride
119413-54-6
Thumb
  • InChI Key: DGHHQBMTXTWTJV-BQAIUKQQSA-N
  • Monoisotopic Mass: 457.1404486
  • Average Mass: 457.907
DBSALT000322
Categories
UNII7M7YKX2N15
CAS number123948-87-8
WeightAverage: 421.4458
Monoisotopic: 421.163770861
Chemical FormulaC23H23N3O5
InChI KeyUCFGDBYHRUNTLO-QHCPKHFHSA-N
InChI
InChI=1S/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
IUPAC Name
(19S)-8-[(dimethylamino)methyl]-19-ethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.0²,¹¹.0⁴,⁹.0¹⁵,²⁰]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
SMILES
CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=C(C=CC(O)=C4CN(C)C)N=C13)C2=O
Pharmacology
IndicationFor the treatment of advanced ovarian cancer in patients with disease that has recurred or progressed following therapy with platinum-based regimens. Also used as a second-line therapy for treatment-sensitive small cell lung cancer, as well as in combination with cisplatin for the treatment of stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment with surgery and/or radiation therapy.
Structured Indications
PharmacodynamicsTopotecan, 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. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can 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 actionTopotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. 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. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death). Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor.
TargetKindPharmacological actionActionsOrganismUniProt ID
DNA topoisomerase 1Proteinyes
inhibitor
HumanP11387 details
DNA topoisomerase I, mitochondrialProteinunknown
inhibitor
HumanQ969P6 details
DNANucleotideyes
intercalation
Humannot applicabledetails
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding35%
Metabolism

Topotecan undergoes a reversible pH dependent hydrolysis of its lactone moiety; it is the lactone form that is pharmacologically active.

Route of eliminationRenal clearance is an important determinant of topotecan elimination. In a mass balance/excretion study in 4 patients with solid tumors, the overall recovery of total topotecan and its N-desmethyl metabolite in urine and feces over 9 days averaged 73.4 ± 2.3% of the administered IV dose. Fecal elimination of total topotecan accounted for 9 ± 3.6% while fecal elimination of N-desmethyl topotecan was 1.7 ± 0.6%.
Half life2-3 hours
ClearanceNot Available
ToxicityThe primary anticipated complication of overdosage would consist of bone marrow suppression.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetaminophenThe serum concentration of Topotecan can be increased when it is combined with Acetaminophen.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Topotecan.Approved
AfatinibThe serum concentration of Topotecan can be increased when it is combined with Afatinib.Approved
AlbendazoleThe serum concentration of Topotecan can be increased when it is combined with Albendazole.Approved, Vet Approved
AldosteroneThe serum concentration of Topotecan can be decreased when it is combined with Aldosterone.Experimental
AlectinibThe serum concentration of Topotecan can be increased when it is combined with Alectinib.Approved
AlfentanilThe serum concentration of Topotecan can be increased when it is combined with Alfentanil.Approved, Illicit
ALT-110The risk or severity of adverse effects can be increased when Topotecan is combined with ALT-110.Investigational
AmantadineThe serum concentration of Topotecan can be increased when it is combined with Amantadine.Approved
Aminohippuric acidThe serum concentration of Topotecan can be increased when it is combined with Aminohippuric acid.Approved
AmiodaroneThe serum concentration of Topotecan can be increased when it is combined with Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Topotecan can be increased when it is combined with Amitriptyline.Approved
AmlodipineThe serum concentration of Topotecan can be increased when it is combined with Amlodipine.Approved
AmprenavirThe serum concentration of Topotecan can be increased when it is combined with Amprenavir.Approved
AmsacrineThe serum concentration of Topotecan can be increased when it is combined with Amsacrine.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of Topotecan.Investigational
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Topotecan.Approved, Investigational
AstemizoleThe serum concentration of Topotecan can be increased when it is combined with Astemizole.Approved, Withdrawn
AtazanavirThe serum concentration of Topotecan can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Topotecan can be increased when it is combined with Atenolol.Approved
AtorvastatinThe serum concentration of Topotecan can be increased when it is combined with Atorvastatin.Approved
AzelastineThe serum concentration of Topotecan can be increased when it is combined with Azelastine.Approved
AzithromycinThe serum concentration of Topotecan can be increased when it is combined with Azithromycin.Approved
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Topotecan.Investigational
BenzocaineThe serum concentration of Topotecan can be increased when it is combined with Benzocaine.Approved
BepridilThe serum concentration of Topotecan can be increased when it is combined with Bepridil.Approved, Withdrawn
BevacizumabBevacizumab may increase the cardiotoxic activities of Topotecan.Approved, Investigational
BiperidenThe serum concentration of Topotecan can be increased when it is combined with Biperiden.Approved
BosutinibThe serum concentration of Topotecan can be increased when it is combined with Bosutinib.Approved
BromocriptineThe serum concentration of Topotecan can be increased when it is combined with Bromocriptine.Approved, Investigational
BuprenorphineThe serum concentration of Topotecan can be increased when it is combined with Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe serum concentration of Topotecan can be increased when it is combined with Buspirone.Approved, Investigational
CabazitaxelThe serum concentration of Topotecan can be increased when it is combined with Cabazitaxel.Approved
CaffeineThe serum concentration of Topotecan can be increased when it is combined with Caffeine.Approved
CanagliflozinThe serum concentration of Topotecan can be increased when it is combined with Canagliflozin.Approved
CandesartanThe serum concentration of Topotecan can be increased when it is combined with Candesartan.Approved
CaptoprilThe serum concentration of Topotecan can be increased when it is combined with Captopril.Approved
CarbamazepineThe serum concentration of Topotecan can be increased when it is combined with Carbamazepine.Approved, Investigational
CarboplatinThe risk or severity of adverse effects can be increased when Carboplatin is combined with Topotecan.Approved
CarvedilolThe serum concentration of Topotecan can be increased when it is combined with Carvedilol.Approved, Investigational
CaspofunginThe serum concentration of Topotecan can be increased when it is combined with Caspofungin.Approved
CDX-110The risk or severity of adverse effects can be increased when Topotecan is combined with CDX-110.Investigational
ChloroquineThe serum concentration of Topotecan can be increased when it is combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe serum concentration of Topotecan can be increased when it is combined with Chlorpromazine.Approved, Vet Approved
ChlorpropamideThe serum concentration of Topotecan can be increased when it is combined with Chlorpropamide.Approved
ChlorprothixeneThe serum concentration of Topotecan can be increased when it is combined with Chlorprothixene.Approved, Withdrawn
CholesterolThe serum concentration of Topotecan can be increased when it is combined with Cholesterol.Experimental
Cholic AcidThe serum concentration of Topotecan can be decreased when it is combined with Cholic Acid.Approved
CilazaprilThe serum concentration of Topotecan can be increased when it is combined with Cilazapril.Approved
CimetidineThe serum concentration of Topotecan can be increased when it is combined with Cimetidine.Approved
CiprofloxacinThe serum concentration of Topotecan can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CisplatinThe risk or severity of adverse effects can be increased when Cisplatin is combined with Topotecan.Approved
CitalopramThe serum concentration of Topotecan can be increased when it is combined with Citalopram.Approved
ClarithromycinThe serum concentration of Topotecan can be increased when it is combined with Clarithromycin.Approved
ClofazimineThe serum concentration of Topotecan can be increased when it is combined with Clofazimine.Approved, Investigational
ClomipramineThe serum concentration of Topotecan can be increased when it is combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe serum concentration of Topotecan can be increased when it is combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Topotecan is combined with Clozapine.Approved
CobicistatThe serum concentration of Topotecan can be increased when it is combined with Cobicistat.Approved
ColchicineThe serum concentration of Topotecan can be increased when it is combined with Colchicine.Approved
ColforsinThe serum concentration of Topotecan can be increased when it is combined with Colforsin.Experimental
CrizotinibThe serum concentration of Topotecan can be increased when it is combined with Crizotinib.Approved
CyclophosphamideThe serum concentration of Topotecan can be increased when it is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe serum concentration of Topotecan can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Topotecan can be increased when it is combined with Dabrafenib.Approved
DaclatasvirThe serum concentration of Topotecan can be increased when it is combined with Daclatasvir.Approved
DactinomycinThe serum concentration of Topotecan can be increased when it is combined with Dactinomycin.Approved
DaidzinThe serum concentration of Topotecan can be increased when it is combined with Daidzin.Experimental
DasabuvirThe serum concentration of Topotecan can be increased when it is combined with Dasabuvir.Approved
DasatinibThe serum concentration of Topotecan can be increased when it is combined with Dasatinib.Approved, Investigational
DaunorubicinThe serum concentration of Topotecan can be increased when it is combined with Daunorubicin.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Topotecan.Approved
DesipramineThe serum concentration of Topotecan can be increased when it is combined with Desipramine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Topotecan.Approved
DesloratadineThe serum concentration of Topotecan can be increased when it is combined with Desloratadine.Approved, Investigational
DexamethasoneThe serum concentration of Topotecan can be increased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextromethorphanThe serum concentration of Topotecan can be increased when it is combined with Dextromethorphan.Approved
DiclofenacThe serum concentration of Topotecan can be increased when it is combined with Diclofenac.Approved, Vet Approved
DiethylstilbestrolThe serum concentration of Topotecan can be increased when it is combined with Diethylstilbestrol.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Topotecan.Approved
DigoxinThe serum concentration of Topotecan can be increased when it is combined with Digoxin.Approved
DihydroergotamineThe serum concentration of Topotecan can be increased when it is combined with Dihydroergotamine.Approved
DiltiazemThe serum concentration of Topotecan can be increased when it is combined with Diltiazem.Approved
DipyridamoleThe serum concentration of Topotecan can be increased when it is combined with Dipyridamole.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Topotecan.Approved, Investigational
DoxazosinThe serum concentration of Topotecan can be increased when it is combined with Doxazosin.Approved
DoxepinThe serum concentration of Topotecan can be increased when it is combined with Doxepin.Approved
DoxorubicinThe serum concentration of Topotecan can be increased when it is combined with Doxorubicin.Approved, Investigational
DronabinolThe serum concentration of Topotecan can be increased when it is combined with Dronabinol.Approved, Illicit
DronedaroneThe serum concentration of Topotecan can be increased when it is combined with Dronedarone.Approved
ElacridarThe serum concentration of Topotecan can be increased when it is combined with Elacridar.Investigational
ElbasvirThe serum concentration of Topotecan can be increased when it is combined with Elbasvir.Approved
EltrombopagThe serum concentration of Topotecan can be increased when it is combined with Eltrombopag.Approved
EnalaprilThe serum concentration of Topotecan can be increased when it is combined with Enalapril.Approved, Vet Approved
EnzalutamideThe serum concentration of Topotecan can be increased when it is combined with Enzalutamide.Approved
ErgonovineThe serum concentration of Topotecan can be increased when it is combined with Ergonovine.Approved
ErgotamineThe serum concentration of Topotecan can be increased when it is combined with Ergotamine.Approved
ErlotinibThe serum concentration of Topotecan can be increased when it is combined with Erlotinib.Approved, Investigational
ErythromycinThe serum concentration of Topotecan can be increased when it is combined with Erythromycin.Approved, Vet Approved
EstradiolThe serum concentration of Topotecan can be increased when it is combined with Estradiol.Approved, Investigational, Vet Approved
EstramustineThe serum concentration of Topotecan can be increased when it is combined with Estramustine.Approved
EstriolThe serum concentration of Topotecan can be decreased when it is combined with Estriol.Approved, Vet Approved
EstroneThe serum concentration of Topotecan can be increased when it is combined with Estrone.Approved
EtoposideThe serum concentration of Topotecan can be increased when it is combined with Etoposide.Approved
EtravirineThe serum concentration of Topotecan can be increased when it is combined with Etravirine.Approved
FelodipineThe serum concentration of Topotecan can be increased when it is combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Topotecan can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe serum concentration of Topotecan can be increased when it is combined with Fexofenadine.Approved
FidaxomicinThe serum concentration of Topotecan can be increased when it is combined with Fidaxomicin.Approved
FilgrastimThe risk or severity of adverse effects can be increased when Filgrastim is combined with Topotecan.Approved
FingolimodTopotecan may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FluconazoleThe serum concentration of Topotecan can be increased when it is combined with Fluconazole.Approved
FluoxetineThe serum concentration of Topotecan can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe serum concentration of Topotecan can be increased when it is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe serum concentration of Topotecan can be increased when it is combined with Fluphenazine.Approved
FlurazepamThe serum concentration of Topotecan can be increased when it is combined with Flurazepam.Approved, Illicit
FluvoxamineThe serum concentration of Topotecan can be increased when it is combined with Fluvoxamine.Approved, Investigational
FosphenytoinThe serum concentration of Topotecan can be decreased when it is combined with Fosphenytoin.Approved
G17DTThe risk or severity of adverse effects can be increased when Topotecan is combined with G17DT.Investigational
GefitinibThe serum concentration of Topotecan can be increased when it is combined with Gefitinib.Approved, Investigational
GenisteinThe serum concentration of Topotecan can be increased when it is combined with Genistein.Investigational
GI-5005The risk or severity of adverse effects can be increased when Topotecan is combined with GI-5005.Investigational
GlyburideThe serum concentration of Topotecan can be increased when it is combined with Glyburide.Approved
GlycerolThe serum concentration of Topotecan can be increased when it is combined with Glycerol.Experimental
Gramicidin DThe serum concentration of Topotecan can be increased when it is combined with Gramicidin D.Approved
GrepafloxacinThe serum concentration of Topotecan can be increased when it is combined with Grepafloxacin.Withdrawn
HaloperidolThe serum concentration of Topotecan can be increased when it is combined with Haloperidol.Approved
HesperetinThe serum concentration of Topotecan can be increased when it is combined with Hesperetin.Approved
HydrocortisoneThe serum concentration of Topotecan can be increased when it is combined with Hydrocortisone.Approved, Vet Approved
IdelalisibThe serum concentration of Topotecan can be increased when it is combined with Idelalisib.Approved
ImatinibThe serum concentration of Topotecan can be increased when it is combined with Imatinib.Approved
ImipramineThe serum concentration of Topotecan can be increased when it is combined with Imipramine.Approved
IndinavirThe serum concentration of Topotecan can be increased when it is combined with Indinavir.Approved
IndomethacinThe serum concentration of Topotecan can be increased when it is combined with Indomethacin.Approved, Investigational
INGN 201The risk or severity of adverse effects can be increased when Topotecan is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Topotecan is combined with INGN 225.Investigational
IsavuconazoniumThe serum concentration of Topotecan can be increased when it is combined with Isavuconazonium.Approved, Investigational
ItraconazoleThe serum concentration of Topotecan can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Topotecan can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Topotecan can be increased when it is combined with Ivermectin.Approved, Vet Approved
KetamineThe serum concentration of Topotecan can be increased when it is combined with Ketamine.Approved, Vet Approved
KetoconazoleThe serum concentration of Topotecan can be increased when it is combined with Ketoconazole.Approved, Investigational
LansoprazoleThe serum concentration of Topotecan can be increased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe serum concentration of Topotecan can be increased when it is combined with Lapatinib.Approved, Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Topotecan is combined with Leflunomide.Approved, Investigational
LevofloxacinThe serum concentration of Topotecan can be increased when it is combined with Levofloxacin.Approved, Investigational
LevothyroxineThe serum concentration of Topotecan can be decreased when it is combined with Levothyroxine.Approved
LidocaineThe serum concentration of Topotecan can be increased when it is combined with Lidocaine.Approved, Vet Approved
LiothyronineThe serum concentration of Topotecan can be decreased when it is combined with Liothyronine.Approved, Vet Approved
LiotrixThe serum concentration of Topotecan can be decreased when it is combined with Liotrix.Approved
LisinoprilThe serum concentration of Topotecan can be increased when it is combined with Lisinopril.Approved, Investigational
LomitapideThe serum concentration of Topotecan can be increased when it is combined with Lomitapide.Approved
LoperamideThe serum concentration of Topotecan can be increased when it is combined with Loperamide.Approved
LopinavirThe serum concentration of Topotecan can be increased when it is combined with Lopinavir.Approved
LoratadineThe serum concentration of Topotecan can be increased when it is combined with Loratadine.Approved
LosartanThe serum concentration of Topotecan can be increased when it is combined with Losartan.Approved
LovastatinThe serum concentration of Topotecan can be increased when it is combined with Lovastatin.Approved, Investigational
LumacaftorThe serum concentration of Topotecan can be decreased when it is combined with Lumacaftor.Approved
MaprotilineThe serum concentration of Topotecan can be increased when it is combined with Maprotiline.Approved
MebendazoleThe serum concentration of Topotecan can be increased when it is combined with Mebendazole.Approved, Vet Approved
MefloquineThe serum concentration of Topotecan can be increased when it is combined with Mefloquine.Approved
Megestrol acetateThe serum concentration of Topotecan can be increased when it is combined with Megestrol acetate.Approved, Vet Approved
MeprobamateThe serum concentration of Topotecan can be increased when it is combined with Meprobamate.Approved, Illicit
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Topotecan.Withdrawn
MethadoneThe serum concentration of Topotecan can be increased when it is combined with Methadone.Approved
MetoprololThe serum concentration of Topotecan can be increased when it is combined with Metoprolol.Approved, Investigational
MibefradilThe serum concentration of Topotecan can be increased when it is combined with Mibefradil.Withdrawn
MiconazoleThe serum concentration of Topotecan can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
MidazolamThe serum concentration of Topotecan can be increased when it is combined with Midazolam.Approved, Illicit
MifepristoneThe serum concentration of Topotecan can be increased when it is combined with Mifepristone.Approved, Investigational
MitomycinThe serum concentration of Topotecan can be increased when it is combined with Mitomycin.Approved
MitoxantroneThe serum concentration of Topotecan can be increased when it is combined with Mitoxantrone.Approved, Investigational
MorphineThe serum concentration of Topotecan can be increased when it is combined with Morphine.Approved, Investigational
NaltrexoneThe serum concentration of Topotecan can be increased when it is combined with Naltrexone.Approved, Investigational, Vet Approved
NaringeninThe serum concentration of Topotecan can be increased when it is combined with Naringenin.Experimental
NatalizumabThe risk or severity of adverse effects can be increased when Topotecan is combined with Natalizumab.Approved, Investigational
NedaplatinThe risk or severity of adverse effects can be increased when Nedaplatin is combined with Topotecan.Approved
NefazodoneThe serum concentration of Topotecan can be decreased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Topotecan can be increased when it is combined with Nelfinavir.Approved
NeostigmineThe serum concentration of Topotecan can be increased when it is combined with Neostigmine.Approved, Vet Approved
NicardipineThe serum concentration of Topotecan can be increased when it is combined with Nicardipine.Approved
NifedipineThe serum concentration of Topotecan can be increased when it is combined with Nifedipine.Approved
NilotinibThe serum concentration of Topotecan can be increased when it is combined with Nilotinib.Approved, Investigational
NisoldipineThe serum concentration of Topotecan can be increased when it is combined with Nisoldipine.Approved
NitrazepamThe serum concentration of Topotecan can be increased when it is combined with Nitrazepam.Approved
NitrendipineThe serum concentration of Topotecan can be increased when it is combined with Nitrendipine.Approved
NorethisteroneThe serum concentration of Topotecan can be decreased when it is combined with Norethisterone.Approved
NOV-002The risk or severity of adverse effects can be increased when NOV-002 is combined with Topotecan.Investigational
NovobiocinThe serum concentration of Topotecan can be increased when it is combined with Novobiocin.Approved, Vet Approved
OmeprazoleThe serum concentration of Topotecan can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
OuabainOuabain may decrease the cardiotoxic activities of Topotecan.Approved
OxaliplatinThe risk or severity of adverse effects can be increased when Oxaliplatin is combined with Topotecan.Approved, Investigational
P-NitrophenolThe serum concentration of Topotecan can be increased when it is combined with P-Nitrophenol.Experimental
PaclitaxelThe serum concentration of Topotecan can be increased when it is combined with Paclitaxel.Approved, Vet Approved
Palmitic AcidThe serum concentration of Topotecan can be increased when it is combined with Palmitic Acid.Experimental
PantoprazoleThe serum concentration of Topotecan can be increased when it is combined with Pantoprazole.Approved
ParoxetineThe serum concentration of Topotecan can be increased when it is combined with Paroxetine.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Topotecan.Approved
PerindoprilThe serum concentration of Topotecan can be increased when it is combined with Perindopril.Approved
PhenobarbitalThe serum concentration of Topotecan can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Topotecan can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Topotecan.Approved, Investigational
PimozideThe serum concentration of Topotecan can be increased when it is combined with Pimozide.Approved
Platelet Activating FactorThe serum concentration of Topotecan can be decreased when it is combined with Platelet Activating Factor.Experimental
PonatinibThe serum concentration of Topotecan can be increased when it is combined with Ponatinib.Approved
PosaconazoleThe serum concentration of Topotecan can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Topotecan can be increased when it is combined with Pravastatin.Approved
PrazosinThe serum concentration of Topotecan can be increased when it is combined with Prazosin.Approved
PrednisoneThe serum concentration of Topotecan can be increased when it is combined with Prednisone.Approved, Vet Approved
ProbenecidThe serum concentration of Topotecan can be increased when it is combined with Probenecid.Approved
ProgesteroneThe serum concentration of Topotecan can be increased when it is combined with Progesterone.Approved, Vet Approved
PromethazineThe serum concentration of Topotecan can be increased when it is combined with Promethazine.Approved
PropafenoneThe serum concentration of Topotecan can be increased when it is combined with Propafenone.Approved
PropranololThe serum concentration of Topotecan can be increased when it is combined with Propranolol.Approved, Investigational
ProtriptylineThe serum concentration of Topotecan can be increased when it is combined with Protriptyline.Approved
QuercetinThe serum concentration of Topotecan can be increased when it is combined with Quercetin.Experimental
QuinacrineThe serum concentration of Topotecan can be increased when it is combined with Quinacrine.Approved
QuinidineThe serum concentration of Topotecan can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Topotecan can be increased when it is combined with Quinine.Approved
RabeprazoleThe serum concentration of Topotecan can be increased when it is combined with Rabeprazole.Approved, Investigational
Rabies vaccineThe risk or severity of adverse effects can be increased when Topotecan is combined with Rabies vaccine.Approved
Rabies vaccineThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Topotecan.Approved
RanitidineThe serum concentration of Topotecan can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Topotecan can be increased when it is combined with Ranolazine.Approved, Investigational
ReboxetineThe serum concentration of Topotecan can be increased when it is combined with Reboxetine.Approved, Investigational
RegorafenibThe serum concentration of Topotecan can be increased when it is combined with Regorafenib.Approved
ReserpineThe serum concentration of Topotecan can be increased when it is combined with Reserpine.Approved
RifampicinThe serum concentration of Topotecan can be increased when it is combined with Rifampicin.Approved
RilpivirineThe serum concentration of Topotecan can be increased when it is combined with Rilpivirine.Approved
RitonavirThe serum concentration of Topotecan can be increased when it is combined with Ritonavir.Approved, Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Topotecan.Approved
RolapitantThe serum concentration of Topotecan can be increased when it is combined with Rolapitant.Approved
SaquinavirThe serum concentration of Topotecan can be increased when it is combined with Saquinavir.Approved, Investigational
SatraplatinThe risk or severity of adverse effects can be increased when Satraplatin is combined with Topotecan.Investigational
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Topotecan.Approved
ScopolamineThe serum concentration of Topotecan can be increased when it is combined with Scopolamine.Approved
SelegilineThe serum concentration of Topotecan can be increased when it is combined with Selegiline.Approved, Investigational, Vet Approved
SertralineThe serum concentration of Topotecan can be increased when it is combined with Sertraline.Approved
SimeprevirThe serum concentration of Topotecan can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Topotecan can be increased when it is combined with Simvastatin.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Topotecan.Approved
SirolimusThe serum concentration of Topotecan can be increased when it is combined with Sirolimus.Approved, Investigational
SorafenibThe serum concentration of Topotecan can be increased when it is combined with Sorafenib.Approved, Investigational
SpironolactoneThe serum concentration of Topotecan can be increased when it is combined with Spironolactone.Approved
SRP 299The risk or severity of adverse effects can be increased when Topotecan is combined with SRP 299.Investigational
St. John's WortThe serum concentration of Topotecan can be decreased when it is combined with St. John's Wort.Nutraceutical
StaurosporineThe serum concentration of Topotecan can be increased when it is combined with Staurosporine.Experimental
StreptozocinThe serum concentration of Topotecan can be decreased when it is combined with Streptozocin.Approved
SulfasalazineThe serum concentration of Topotecan can be increased when it is combined with Sulfasalazine.Approved
SulfinpyrazoneThe serum concentration of Topotecan can be increased when it is combined with Sulfinpyrazone.Approved
SumatriptanThe serum concentration of Topotecan can be increased when it is combined with Sumatriptan.Approved, Investigational
SunitinibThe serum concentration of Topotecan can be increased when it is combined with Sunitinib.Approved, Investigational
TacrineThe serum concentration of Topotecan can be increased when it is combined with Tacrine.Withdrawn
TacrolimusThe serum concentration of Topotecan can be increased when it is combined with Tacrolimus.Approved, Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Topotecan.Approved, Investigational
TamoxifenThe serum concentration of Topotecan can be increased when it is combined with Tamoxifen.Approved
Taurocholic AcidThe serum concentration of Topotecan can be increased when it is combined with Taurocholic Acid.Experimental
TelmisartanThe serum concentration of Topotecan can be increased when it is combined with Telmisartan.Approved, Investigational
TemsirolimusThe serum concentration of Topotecan can be increased when it is combined with Temsirolimus.Approved
TerazosinThe serum concentration of Topotecan can be increased when it is combined with Terazosin.Approved
TerfenadineThe serum concentration of Topotecan can be increased when it is combined with Terfenadine.Withdrawn
TeriflunomideThe serum concentration of Topotecan can be increased when it is combined with Teriflunomide.Approved
TesmilifeneThe serum concentration of Topotecan can be decreased when it is combined with Tesmilifene.Investigational
TestosteroneThe serum concentration of Topotecan can be increased when it is combined with Testosterone.Approved, Investigational
TG4010The risk or severity of adverse effects can be increased when Topotecan is combined with TG4010.Investigational
TicagrelorThe serum concentration of Topotecan can be increased when it is combined with Ticagrelor.Approved
TofacitinibTopotecan may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TolvaptanThe serum concentration of Topotecan can be increased when it is combined with Tolvaptan.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Topotecan.Approved, Investigational
TrazodoneThe serum concentration of Topotecan can be decreased when it is combined with Trazodone.Approved, Investigational
TrifluoperazineThe serum concentration of Topotecan can be increased when it is combined with Trifluoperazine.Approved
TriflupromazineThe serum concentration of Topotecan can be increased when it is combined with Triflupromazine.Approved, Vet Approved
TrimethoprimThe serum concentration of Topotecan can be increased when it is combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe serum concentration of Topotecan can be increased when it is combined with Trimipramine.Approved
TroleandomycinThe serum concentration of Topotecan can be increased when it is combined with Troleandomycin.Approved
VandetanibThe serum concentration of Topotecan can be increased when it is combined with Vandetanib.Approved
VenlafaxineThe serum concentration of Topotecan can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Topotecan can be increased when it is combined with Verapamil.Approved
VinblastineThe serum concentration of Topotecan can be increased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Topotecan can be increased when it is combined with Vincristine.Approved, Investigational
VinorelbineThe serum concentration of Topotecan can be increased when it is combined with Vinorelbine.Approved, Investigational
VismodegibThe serum concentration of Topotecan can be increased when it is combined with Vismodegib.Approved
ZimelidineThe serum concentration of Topotecan can be increased when it is combined with Zimelidine.Withdrawn
Food InteractionsNot Available
References
Synthesis Reference

Venkata Raghavendra Palle, Sekhar Nariyam, Lankeshwara Matti, “PROCESS FOR PREPARING TOPOTECAN.” U.S. Patent US20070149783, issued June 28, 2007.

US20070149783
General References
  1. Kollmannsberger C, Mross K, Jakob A, Kanz L, Bokemeyer C: Topotecan - A novel topoisomerase I inhibitor: pharmacology and clinical experience. Oncology. 1999;56(1):1-12. [PubMed:9885371 ]
  2. Herben VM, ten Bokkel Huinink WW, Beijnen JH: Clinical pharmacokinetics of topotecan. Clin Pharmacokinet. 1996 Aug;31(2):85-102. [PubMed:8853931 ]
  3. Dennis MJ, Beijnen JH, Grochow LB, van Warmerdam LJ: An overview of the clinical pharmacology of topotecan. Semin Oncol. 1997 Feb;24(1 Suppl 5):S5-12-S5-18. [PubMed:9122737 ]
External Links
ATC CodesL01XX17
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (78.6 KB)
MSDSDownload (29.3 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8911
Blood Brain Barrier-0.9659
Caco-2 permeable-0.6966
P-glycoprotein substrateSubstrate0.7918
P-glycoprotein inhibitor INon-inhibitor0.6121
P-glycoprotein inhibitor IINon-inhibitor0.9507
Renal organic cation transporterNon-inhibitor0.9
CYP450 2C9 substrateNon-substrate0.8844
CYP450 2D6 substrateNon-substrate0.8168
CYP450 3A4 substrateSubstrate0.6875
CYP450 1A2 substrateInhibitor0.5572
CYP450 2C9 inhibitorNon-inhibitor0.8305
CYP450 2D6 inhibitorNon-inhibitor0.8918
CYP450 2C19 inhibitorNon-inhibitor0.824
CYP450 3A4 inhibitorNon-inhibitor0.6464
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7184
Ames testNon AMES toxic0.6516
CarcinogenicityNon-carcinogens0.8504
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.0075 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9963
hERG inhibition (predictor II)Non-inhibitor0.8302
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
CapsuleOral.25 mg/1
CapsuleOral0.25 mg
CapsuleOral1 mg
CapsuleOral1 mg/1
Injection, powder, lyophilized, for solutionIntravenous4 mg/4mL
Powder, for solutionIntravenous1 mg
Injection, powder, for solutionIntravenous1 mg
Injection, powder, for solutionIntravenous4 mg
InjectionIntravenous1 mg/mL
Injection, solution, concentrateIntravenous1 mg/mL
Powder, for solutionIntravenous4 mg
Injection, powder, for solutionIntravenous4 mg/4mL
Injection, powder, lyophilized, for solutionIntravenous4 mg/mL
SolutionIntravenous1 mg
Injection, solution, concentrateIntravenous1 mg/1ml
Injection, solution, concentrateIntravenous4 mg/4ml
Prices
Unit descriptionCostUnit
Hycamtin 4 mg vial1306.1USD vial
Hycamtin 1 mg capsule358.92USD capsule
Hycamtin 0.25 mg capsule89.73USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2103707 No2003-12-092012-02-07Canada
CA2103708 No2004-04-272012-02-07Canada
US5004758 No1993-05-282010-05-28Us
US5674872 No1995-04-072015-04-07Us
US8158645 No2004-12-102024-12-10Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point213-218 °CNot Available
water solubility1 mg/mlNot Available
logP0.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.861 mg/mLALOGPS
logP1.84ALOGPS
logP-0.36ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)8ChemAxon
pKa (Strongest Basic)9.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area103.2 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity115.02 m3·mol-1ChemAxon
Polarizability44.86 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as camptothecins. These are heterocyclic compounds comprising a planar pentacyclic ring structure, that includes a pyrrolo[3,4-beta]-quinoline moiety (rings A, B and C), conjugated pyridone moiety (ring D) and one chiral center at position 20 within the alpha-hydroxy lactone ring with (S) configuration (the E-ring).
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassCamptothecins
Sub ClassNot Available
Direct ParentCamptothecins
Alternative Parents
Substituents
  • Camptothecin
  • Hydroxyquinoline
  • Quinoline
  • Pyranopyridine
  • Benzylamine
  • Aralkylamine
  • Pyridinone
  • Benzenoid
  • Pyridine
  • Heteroaromatic compound
  • Tertiary alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Lactone
  • Lactam
  • Carboxylic acid ester
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Poly(a) rna binding
Specific Function:
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphot...
Gene Name:
TOP1
Uniprot ID:
P11387
Molecular Weight:
90725.19 Da
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:11166732 ]
  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:11443926 ]
  3. 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:12437383 ]
  4. 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:12520736 ]
  5. 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:12855624 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Kollmannsberger C, Mross K, Jakob A, Kanz L, Bokemeyer C: Topotecan - A novel topoisomerase I inhibitor: pharmacology and clinical experience. Oncology. 1999;56(1):1-12. [PubMed:9885371 ]
  8. Herben VM, ten Bokkel Huinink WW, Beijnen JH: Clinical pharmacokinetics of topotecan. Clin Pharmacokinet. 1996 Aug;31(2):85-102. [PubMed:8853931 ]
  9. Dennis MJ, Beijnen JH, Grochow LB, van Warmerdam LJ: An overview of the clinical pharmacology of topotecan. Semin Oncol. 1997 Feb;24(1 Suppl 5):S5-12-S5-18. [PubMed:9122737 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function:
Releases the supercoiling and torsional tension of DNA introduced during duplication of mitochondrial DNA by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosy...
Gene Name:
TOP1MT
Uniprot ID:
Q969P6
Molecular Weight:
69871.39 Da
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:8390858 ]
3. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB Jr, Stewart L: The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15387-92. Epub 2002 Nov 8. [PubMed:12426403 ]
  2. Pourquier P, Takebayashi Y, Urasaki Y, Gioffre C, Kohlhagen G, Pommier Y: Induction of topoisomerase I cleavage complexes by 1-beta -D-arabinofuranosylcytosine (ara-C) in vitro and in ara-C-treated cells. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1885-90. [PubMed:10677551 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitorinducer
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Houghton PJ, Germain GS, Harwood FC, Schuetz JD, Stewart CF, Buchdunger E, Traxler P: Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res. 2004 Apr 1;64(7):2333-7. [PubMed:15059881 ]
  2. Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, van Waardenburg RC, de Jong LA, Pluim D, Beijnen JH, Schellens JH: Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res. 2001 Apr;7(4):935-41. [PubMed:11309344 ]
  3. Sugimoto Y, Tsukahara S, Imai Y, Sugimoto Y, Ueda K, Tsuruo T: Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol Cancer Ther. 2003 Jan;2(1):105-12. [PubMed:12533678 ]
  4. 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:10493507 ]
  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:11036110 ]
  6. Allen JD, Van Dort SC, Buitelaar M, van Tellingen O, Schinkel AH: Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res. 2003 Mar 15;63(6):1339-44. [PubMed:12649196 ]
  7. Breedveld P, Zelcer N, Pluim D, Sonmezer O, Tibben MM, Beijnen JH, Schinkel AH, van Tellingen O, Borst P, Schellens JH: Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res. 2004 Aug 15;64(16):5804-11. [PubMed:15313923 ]
  8. Carcaboso AM, Elmeliegy MA, Shen J, Juel SJ, Zhang ZM, Calabrese C, Tracey L, Waters CM, Stewart CF: Tyrosine kinase inhibitor gefitinib enhances topotecan penetration of gliomas. Cancer Res. 2010 Jun 1;70(11):4499-508. doi: 10.1158/0008-5472.CAN-09-4264. Epub 2010 May 11. [PubMed:20460504 ]
  9. Shen J, Carcaboso AM, Hubbard KE, Tagen M, Wynn HG, Panetta JC, Waters CM, Elmeliegy MA, Stewart CF: Compartment-specific roles of ATP-binding cassette transporters define differential topotecan distribution in brain parenchyma and cerebrospinal fluid. Cancer Res. 2009 Jul 15;69(14):5885-92. doi: 10.1158/0008-5472.CAN-09-0700. Epub 2009 Jun 30. [PubMed:19567673 ]
  10. 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:10777678 ]
  11. 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:10912951 ]
  12. 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:10930538 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Collett A, Tanianis-Hughes J, Hallifax D, Warhurst G: Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res. 2004 May;21(5):819-26. [PubMed:15180340 ]
  2. Carcaboso AM, Elmeliegy MA, Shen J, Juel SJ, Zhang ZM, Calabrese C, Tracey L, Waters CM, Stewart CF: Tyrosine kinase inhibitor gefitinib enhances topotecan penetration of gliomas. Cancer Res. 2010 Jun 1;70(11):4499-508. doi: 10.1158/0008-5472.CAN-09-4264. Epub 2010 May 11. [PubMed:20460504 ]
  3. Shen J, Carcaboso AM, Hubbard KE, Tagen M, Wynn HG, Panetta JC, Waters CM, Elmeliegy MA, Stewart CF: Compartment-specific roles of ATP-binding cassette transporters define differential topotecan distribution in brain parenchyma and cerebrospinal fluid. Cancer Res. 2009 Jul 15;69(14):5885-92. doi: 10.1158/0008-5472.CAN-09-0700. Epub 2009 Jun 30. [PubMed:19567673 ]
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Drug created on June 13, 2005 07:24 / Updated on December 10, 2016 02:39