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Identification
NameTeniposide
Accession NumberDB00444  (APRD00649)
TypeSmall Molecule
GroupsApproved
Description

A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle. [PubChem]

Structure
Thumb
Synonyms
4'-demethylepipodophyllotoxin 9-(4,6-O-(R)-2-thenylidene-beta-D-glucopyranoside)
Epidophyllotoxin
Teniposid
Téniposide
Teniposido
Teniposidum
External Identifiers
  • EPT
  • PGT
  • VM-26
  • VM26
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Teniposideinjection, solution10 mg/mLintravenousWG Critical Care, LLC2013-04-30Not applicableUs
Vumonliquid10 mgintravenousBristol Myers Squibb Canada1984-12-31Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
Bang LaiDouble-Crane
Brand mixturesNot Available
SaltsNot Available
Categories
UNII957E6438QA
CAS number29767-20-2
WeightAverage: 656.654
Monoisotopic: 656.1563618
Chemical FormulaC32H32O13S
InChI KeyNRUKOCRGYNPUPR-QBPJDGROSA-N
InChI
InChI=1S/C32H32O13S/c1-37-19-6-13(7-20(38-2)25(19)33)23-14-8-17-18(42-12-41-17)9-15(14)28(16-10-39-30(36)24(16)23)44-32-27(35)26(34)29-21(43-32)11-40-31(45-29)22-4-3-5-46-22/h3-9,16,21,23-24,26-29,31-35H,10-12H2,1-2H3/t16-,21+,23+,24-,26+,27+,28+,29+,31+,32-/m0/s1
IUPAC Name
(10R,11R,15R,16S)-16-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-(thiophen-2-yl)-hexahydro-2H-pyrano[3,2-d][1,3]dioxin-6-yl]oxy}-10-(4-hydroxy-3,5-dimethoxyphenyl)-4,6,13-trioxatetracyclo[7.7.0.0³,⁷.0¹¹,¹⁵]hexadeca-1,3(7),8-trien-12-one
SMILES
[H][C@]12COC(=O)[C@]1([H])[C@]([H])(C1=CC(OC)=C(O)C(OC)=C1)C1=CC3=C(OCO3)C=C1[C@@]2([H])O[C@]1([H])O[C@]2([H])CO[C@]([H])(O[C@@]2([H])[C@]([H])(O)[C@@]1([H])O)C1=CC=CS1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as podophyllotoxins. These are tetralin lignans in which the benzene moiety of the tetralin skeleton is fused to a 1,3-dioxolane and the cyclohexane is fused to a butyrolactone (pyrrolidin-2-one).
KingdomOrganic compounds
Super ClassLignans, neolignans and related compounds
ClassLignan lactones
Sub ClassPodophyllotoxins
Direct ParentPodophyllotoxins
Alternative Parents
Substituents
  • Podophyllotoxin
  • 1-aryltetralin lignan
  • M-dimethoxybenzene
  • Dimethoxybenzene
  • Tetralin
  • Pyranodioxin
  • Methoxyphenol
  • Benzodioxole
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • Phenol
  • Alkyl aryl ether
  • Benzenoid
  • Oxane
  • Monosaccharide
  • Gamma butyrolactone
  • Monocyclic benzene moiety
  • Meta-dioxane
  • Heteroaromatic compound
  • Thiophene
  • Oxolane
  • Secondary alcohol
  • Lactone
  • Carboxylic acid ester
  • 1,2-diol
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid derivative
  • Acetal
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationTeniposide is used for the treatment of refractory acute lymphoblastic leukaemia
PharmacodynamicsTeniposide is a phase-specific cytotoxic drug, acting in the late S or early G 2 phase of the cell cycle, thus preventing cells from entering mitosis. Teniposide causes dose-dependent single- and double-stranded breaks in DNA and DNA: protein cross-links.
Mechanism of actionThe mechanism of action appears to be related to the inhibition of type II topoisomerase activity since teniposide does not intercalate into DNA or bind strongly to DNA. Teniposide binds to and inhibits DNA topoisomerase II. The cytotoxic effects of teniposide are related to the relative number of double-stranded DNA breaks produced in cells, which are a reflection of the stabilization of a topoisomerase II-DNA intermediate.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
SubstrateEnzymesProduct
Teniposide
Teniposide catechol derivativeDetails
Teniposide catechol derivative
Teniposide o-quinone derivativeDetails
Route of eliminationFrom 4% to 12% of a dose is excreted in urine as parent drug. Fecal excretion of radioactivity within 72 hours after dosing accounted for 0% to 10% of the dose.
Half life5 hours
Clearance
  • 10.3 mL/min/m2
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Teniposide Metabolism PathwayDrug metabolismSMP00602
Teniposide Action PathwayDrug actionSMP00443
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8166
Blood Brain Barrier-0.9584
Caco-2 permeable-0.5728
P-glycoprotein substrateSubstrate0.6638
P-glycoprotein inhibitor INon-inhibitor0.8656
P-glycoprotein inhibitor IINon-inhibitor0.9094
Renal organic cation transporterNon-inhibitor0.8549
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5599
CYP450 1A2 substrateNon-inhibitor0.7516
CYP450 2C9 inhibitorNon-inhibitor0.5445
CYP450 2D6 inhibitorNon-inhibitor0.7197
CYP450 2C19 inhibitorInhibitor0.7423
CYP450 3A4 inhibitorInhibitor0.7677
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.798
Ames testAMES toxic0.7291
CarcinogenicityNon-carcinogens0.9303
BiodegradationNot ready biodegradable0.9254
Rat acute toxicity2.8354 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9934
hERG inhibition (predictor II)Non-inhibitor0.8415
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb co pharmaceutical research institute
Packagers
Dosage forms
FormRouteStrength
Injection, solutionintravenous10 mg/mL
Liquidintravenous10 mg
Prices
Unit descriptionCostUnit
Vumon 10 mg/ml ampul75.31USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point242-246 °CPhysProp
logP1.24HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0598 mg/mLALOGPS
logP2.78ALOGPS
logP2.78ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)9.33ChemAxon
pKa (Strongest Basic)-3.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area160.83 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity155.61 m3·mol-1ChemAxon
Polarizability64.84 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesL01CB02
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (46.6 KB)
Interactions
Drug Interactions
Drug
AmobarbitalThe serum concentration of Teniposide can be decreased when it is combined with Amobarbital.
AprepitantThe serum concentration of Teniposide can be increased when it is combined with Aprepitant.
BexaroteneThe serum concentration of Teniposide can be decreased when it is combined with Bexarotene.
BosentanThe serum concentration of Teniposide can be decreased when it is combined with Bosentan.
ButabarbitalThe serum concentration of Teniposide can be decreased when it is combined with Butabarbital.
ButethalThe serum concentration of Teniposide can be decreased when it is combined with Butethal.
ClozapineThe risk or severity of adverse effects can be increased when Teniposide is combined with Clozapine.
ConivaptanThe serum concentration of Teniposide can be increased when it is combined with Conivaptan.
DabrafenibThe serum concentration of Teniposide can be decreased when it is combined with Dabrafenib.
DasatinibThe serum concentration of Teniposide can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Teniposide can be decreased when it is combined with Deferasirox.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Teniposide.
FluconazoleThe metabolism of Teniposide can be decreased when combined with Fluconazole.
FosaprepitantThe serum concentration of Teniposide can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Teniposide can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Teniposide can be increased when it is combined with Fusidic Acid.
HeptabarbitalThe serum concentration of Teniposide can be decreased when it is combined with Heptabarbital.
HexobarbitalThe serum concentration of Teniposide can be decreased when it is combined with Hexobarbital.
IdelalisibThe serum concentration of Teniposide can be increased when it is combined with Idelalisib.
IvacaftorThe serum concentration of Teniposide can be increased when it is combined with Ivacaftor.
LeflunomideThe risk or severity of adverse effects can be increased when Teniposide is combined with Leflunomide.
LuliconazoleThe serum concentration of Teniposide can be increased when it is combined with Luliconazole.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Teniposide.
MethohexitalThe serum concentration of Teniposide can be decreased when it is combined with Methohexital.
MifepristoneThe serum concentration of Teniposide can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Teniposide can be decreased when it is combined with Mitotane.
NatalizumabThe risk or severity of adverse effects can be increased when Teniposide is combined with Natalizumab.
NelfinavirThe metabolism of Teniposide can be decreased when combined with Nelfinavir.
NetupitantThe serum concentration of Teniposide can be increased when it is combined with Netupitant.
PalbociclibThe serum concentration of Teniposide can be increased when it is combined with Palbociclib.
PentobarbitalThe serum concentration of Teniposide can be decreased when it is combined with Pentobarbital.
PhenobarbitalThe serum concentration of Teniposide can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Teniposide can be decreased when it is combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Teniposide.
PrimidoneThe serum concentration of Teniposide can be decreased when it is combined with Primidone.
RanolazineThe serum concentration of Teniposide can be increased when it is combined with Ranolazine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Teniposide.
SaquinavirThe serum concentration of Teniposide can be increased when it is combined with Saquinavir.
SecobarbitalThe serum concentration of Teniposide can be decreased when it is combined with Secobarbital.
SiltuximabThe serum concentration of Teniposide can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Teniposide can be increased when it is combined with Simeprevir.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Teniposide.
St. John's WortThe serum concentration of Teniposide can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Teniposide can be increased when it is combined with Stiripentol.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Teniposide.
TesmilifeneThe serum concentration of Teniposide can be decreased when it is combined with Tesmilifene.
TocilizumabThe serum concentration of Teniposide can be decreased when it is combined with Tocilizumab.
TofacitinibTeniposide may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Teniposide.
VerapamilThe serum concentration of Teniposide can be increased when it is combined with Verapamil.
VincristineTeniposide may increase the neurotoxic activities of Vincristine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ubiquitin binding
Specific Function:
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
Molecular Weight:
174383.88 Da
References
  1. de Lucio B, Manuel V, Barrera-Rodriguez R: Characterization of human NSCLC cell line with innate etoposide-resistance mediated by cytoplasmic localization of topoisomerase II alpha. Cancer Sci. 2005 Nov;96(11):774-83. [PubMed:16271071 ]
  2. Uesaka T, Shono T, Kuga D, Suzuki SO, Niiro H, Miyamoto K, Matsumoto K, Mizoguchi M, Ohta M, Iwaki T, Sasaki T: Enhanced expression of DNA topoisomerase II genes in human medulloblastoma and its possible association with etoposide sensitivity. J Neurooncol. 2007 Sep;84(2):119-29. Epub 2007 Mar 15. [PubMed:17361331 ]
  3. Winnicka K, Bielawski K, Bielawska A: Cardiac glycosides in cancer research and cancer therapy. Acta Pol Pharm. 2006 Mar-Apr;63(2):109-15. [PubMed:17514873 ]
  4. Faure P, Madelaine I: [Topoisomerases: therapeutic value]. Ann Pharm Fr. 1996;54(1):40-4. [PubMed:8702194 ]
  5. Umanskaya ON, Ioudinkova ES, Razin SV, Bystritskiy AA: Inhibition of DNA topoisomerase II in living cells stimulates illegitimate recombination. Dokl Biochem Biophys. 2005 Nov-Dec;405:423-5. [PubMed:16480143 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 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 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 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
substrate
General Function:
Transporter activity
Specific Function:
Isoform 1: May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS).Isoform 2: Inhibits TNF-alpha-mediated apoptosis through blocking one or more caspases.
Gene Name:
ABCC6
Uniprot ID:
O95255
Molecular Weight:
164904.81 Da
References
  1. Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD: Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002 Nov 1;62(21):6172-7. [PubMed:12414644 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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. 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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23