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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
SynonymLanguageCode
EpidophyllotoxinNot AvailableIS
TeniposidGermanINN
TéniposideFrench/ItalianINN/DCIT
TeniposidoSpanishINN
TeniposidumLatinINN
SaltsNot Available
Brand names
NameCompany
Bang LaiDouble-Crane
VumonBristol-Myers Squibb
Brand mixturesNot Available
Categories
CAS number29767-20-2
WeightAverage: 656.654
Monoisotopic: 656.1563618
Chemical FormulaC32H32O13S
InChI KeyNRUKOCRGYNPUPR-PSZSYXFXSA-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-{[(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[7.7.0.0^{3,7}.0^{11,15}]hexadeca-1(9),2,7-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@H]2O[C@@H]1O[C@]2([H])COC(O[C@@]2([H])[C@H](O)[C@H]1O)C1=CC=CS1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLignans and Norlignans
ClassLignan Lactones
SubclassPodophyllotoxins
Direct parentPodophyllotoxins
Alternative parentsArylnaphthalene Lignans; Tetralin Lignans; Methoxyphenols and Derivatives; Tetralins; Pyranodioxins; Benzodioxoles; Anisoles; Alkyl Aryl Ethers; Oxanes; 1,3-Dioxanes; Oxolanes; Tetrahydrofurans; Thiophenes; Lactones; 1,2-Diols; Secondary Alcohols; Carboxylic Acid Esters; Polyamines; Acetals; Enols; Dialkyl Ethers
Substituentsarylnaphthalene lignan skeleton; tetralin lignan skeleton; pyranodioxin; methoxyphenol; tetralin; benzodioxole; anisole; phenol ether; phenol derivative; alkyl aryl ether; benzene; gamma butyrolactone; meta-dioxane; oxane; oxolane; thiophene; tetrahydrofuran; carboxylic acid ester; 1,2-diol; lactone; secondary alcohol; carboxylic acid derivative; polyamine; dialkyl ether; acetal; enol; ether; alcohol
Classification descriptionThis compound belongs to the 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).
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.
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 Action PathwayDrug actionSMP00443
Teniposide Metabolism PathwayDrug metabolismSMP00602
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8166
Blood Brain Barrier - 0.9584
Caco-2 permeable - 0.5728
P-glycoprotein substrate Substrate 0.6638
P-glycoprotein inhibitor I Non-inhibitor 0.8656
P-glycoprotein inhibitor II Non-inhibitor 0.9094
Renal organic cation transporter Non-inhibitor 0.8549
CYP450 2C9 substrate Non-substrate 0.7897
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.5599
CYP450 1A2 substrate Non-inhibitor 0.7516
CYP450 2C9 substrate Non-inhibitor 0.5445
CYP450 2D6 substrate Non-inhibitor 0.7197
CYP450 2C19 substrate Inhibitor 0.7423
CYP450 3A4 substrate Inhibitor 0.7677
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.798
Ames test AMES toxic 0.7291
Carcinogenicity Non-carcinogens 0.9303
Biodegradation Not ready biodegradable 0.9254
Rat acute toxicity 2.8354 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9934
hERG inhibition (predictor II) Non-inhibitor 0.8415
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb co pharmaceutical research institute
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous
Prices
Unit descriptionCostUnit
Vumon 10 mg/ml ampul75.31USDml
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 solubility5.98e-02 g/lALOGPS
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 area160.83ChemAxon
rotatable bond count6ChemAxon
refractivity155.61ChemAxon
polarizability65.8ChemAxon
number of rings8ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD02698
KEGG CompoundC11153
PubChem Compound34698
PubChem Substance46507536
ChemSpider31930
Therapeutic Targets DatabaseDAP000651
PharmGKBPA451611
Drug Product Database588989
RxListhttp://www.rxlist.com/cgi/generic2/teniposide.htm
Drugs.comhttp://www.drugs.com/cdi/teniposide.html
WikipediaTeniposide
ATC CodesL01CB02
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(46.6 KB)
Interactions
Drug Interactions
Drug
AmprenavirThe strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Amprenavir is initiated, discontinued or dose changed.
AtazanavirThe strong CYP3A4 inhibitor, Atazanavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Atazanavir is initiated, discontinued or dose changed.
ButabarbitalBarbiturates like butabarbital may decrease the serum concentration of Teniposide. arbiturates may decrease the serum concentration of Teniposide.
ButalbitalBarbiturates such as butalbital may decrease the serum concentration of teniposide. Consider alternatives to combined treatment with barbiturates and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely.
ClarithromycinThe strong CYP3A4 inhibitor, Clarithromycin, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Clarithromycin is initiated, discontinued or dose changed.
ConivaptanThe strong CYP3A4 inhibitor, Conivaptan, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Conivaptan is initiated, discontinued or dose changed.
DarunavirThe strong CYP3A4 inhibitor, Darunavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Darunavir is initiated, discontinued or dose changed.
DelavirdineThe strong CYP3A4 inhibitor, Delavirdine, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Delavirdine is initiated, discontinued or dose changed.
FosamprenavirThe strong CYP3A4 inhibitor, Fosamprenavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Fosamprenavir is initiated, discontinued or dose changed.
ImatinibThe strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Imatinib is initiated, discontinued or dose changed.
IndinavirThe strong CYP3A4 inhibitor, Indinavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Indinavir is initiated, discontinued or dose changed.
IsoniazidThe strong CYP3A4 inhibitor, Isoniazid, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Isoniazid is initiated, discontinued or dose changed.
ItraconazoleThe strong CYP3A4 inhibitor, Itraconazole, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Itraconazole is initiated, discontinued or dose changed.
KetoconazoleThe strong CYP3A4 inhibitor, Ketoconazole, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Ketoconazole is initiated, discontinued or dose changed.
LopinavirThe strong CYP3A4 inhibitor, Lopinavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Lopinavir is initiated, discontinued or dose changed.
MiconazoleThe strong CYP3A4 inhibitor, Miconazole, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Miconazole is initiated, discontinued or dose changed.
NatalizumabThe immunosuppressant, Teniposide, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
NefazodoneThe strong CYP3A4 inhibitor, Nefazodone, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Nefazodone is initiated, discontinued or dose changed.
NelfinavirThe strong CYP3A4 inhibitor, Nelfinavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Nelfinavir is initiated, discontinued or dose changed.
NicardipineThe strong CYP3A4 inhibitor, Nicardipine, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Nicardipine is initiated, discontinued or dose changed.
PosaconazoleThe strong CYP3A4 inhibitor, Posaconazole, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Posaconazole is initiated, discontinued or dose changed.
QuinidineThe strong CYP3A4 inhibitor, Quinidine, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Quinidine is initiated, discontinued or dose changed.
QuinupristinThis combination presents an increased risk of toxicity
RitonavirThe strong CYP3A4 inhibitor, Ritonavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Ritonavir is initiated, discontinued or dose changed.
SaquinavirThe strong CYP3A4 inhibitor, Saquinavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Saquinavir is initiated, discontinued or dose changed.
TelithromycinThe strong CYP3A4 inhibitor, Telithromycin, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Telithromycin is initiated, discontinued or dose changed.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
VoriconazoleThe strong CYP3A4 inhibitor, Voriconazole, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Voriconazole is initiated, discontinued or dose changed.
Food InteractionsNot Available

Targets

1. DNA topoisomerase 2-alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA topoisomerase 2-alpha P11388 Details

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
  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
  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
  4. Faure P, Madelaine I: [Topoisomerases: therapeutic value] Ann Pharm Fr. 1996;54(1):40-4. Pubmed
  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
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

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. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance-associated protein 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance-associated protein 6 O95255 Details

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

2. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

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

Comments
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Drug created on June 13, 2005 07:24 / Updated on March 06, 2014 11:58