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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
4'-Demethylepipodophyllotoxin 9-(4,6-O-2-thenylidene-beta-D-glucopyranoside)Not AvailableNot Available
4'-Demethylepipodophyllotoxin-beta-D-thenylidene glucosideNot AvailableNot Available
EpidophyllotoxinNot AvailableIS
HSDB 6546Not AvailableNot Available
NSC 122819Not AvailableNot Available
NSC-122819Not AvailableNot Available
TeniposidGermanINN
TéniposideFrench/ItalianINN/DCIT
TeniposidoSpanishINN
TeniposidumLatinINN
VM-26Not AvailableNot Available
VumonNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Vumoninjection, solution10 mg/mLintravenousE.R. Squibb & Sons, L.L.C.1992-07-142015-07-14Us 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Teniposideinjection, solution10 mg/mLintravenousWG Critical Care, LLC2013-04-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vumonliquid10 mgintravenousBristol Myers Squibb CanadaNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
Bang LaiDouble-Crane
Brand mixturesNot Available
SaltsNot 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[7.7.0.0³,⁷.0¹¹,¹⁵]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@H]2O[C@@H]1O[C@]2([H])COC(O[C@@]2([H])[C@H](O)[C@H]1O)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
  • Tetralin
  • Pyranodioxin
  • Methoxyphenol
  • Benzodioxole
  • Phenol ether
  • Anisole
  • Phenol
  • Alkyl aryl ether
  • Oxane
  • Monosaccharide
  • Gamma butyrolactone
  • 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 Descriptors
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
PathwaysNot Available
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 substrateNon-inhibitor0.5445
CYP450 2D6 substrateNon-inhibitor0.7197
CYP450 2C19 substrateInhibitor0.7423
CYP450 3A4 substrateInhibitor0.7677
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
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
Polarizability65.8 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 ReferenceNot Available
External Links
ATC CodesL01CB02
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (46.6 KB)
Interactions
Drug Interactions
Drug
AmobarbitalBarbiturates may decrease the serum concentration of Teniposide.
AprepitantMay increase the serum concentration of CYP3A4 Substrates.
AripiprazoleCYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole.
BosentanMay decrease the serum concentration of CYP3A4 Substrates.
ButabarbitalBarbiturates may decrease the serum concentration of Teniposide.
ButalbitalBarbiturates may decrease the serum concentration of Teniposide.
ButethalMay decrease the serum concentration of Teniposide.
ClozapineMyelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for agranulocytosis may be increased.
ConivaptanMay increase the serum concentration of CYP3A4 Substrates.
DabrafenibMay decrease the serum concentration of CYP3A4 Substrates.
DasatinibMay increase the serum concentration of CYP3A4 Substrates.
DeferasiroxMay decrease the serum concentration of CYP3A4 Substrates.
DenosumabMay enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
DofetilideCYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide.
FosaprepitantMay increase the serum concentration of CYP3A4 Substrates.
FosphenytoinMay decrease the serum concentration of Teniposide.
HeptabarbitalMay decrease the serum concentration of Teniposide.
HexobarbitalMay decrease the serum concentration of Teniposide.
HydrocodoneCYP3A4 Inhibitors (Weak) may increase the serum concentration of Hydrocodone.
IvacaftorMay increase the serum concentration of CYP3A4 Substrates.
LeflunomideImmunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased.
LomitapideCYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide.
LULICONAZOLEMay increase the serum concentration of CYP3A4 Substrates.
MethohexitalMay decrease the serum concentration of Teniposide.
MifepristoneMay increase the serum concentration of CYP3A4 Substrates.
MitotaneMay decrease the serum concentration of CYP3A4 Substrates.
NatalizumabImmunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
PentobarbitalBarbiturates may decrease the serum concentration of Teniposide.
PhenobarbitalBarbiturates may decrease the serum concentration of Teniposide.
PhenytoinPhenytoin may decrease the serum concentration of Teniposide.
PimecrolimusMay enhance the adverse/toxic effect of Immunosuppressants.
PimozideCYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide.
PrimidoneMay decrease the serum concentration of Teniposide.
RoflumilastMay enhance the immunosuppressive effect of Immunosuppressants.
SecobarbitalBarbiturates may decrease the serum concentration of Teniposide.
SiltuximabMay decrease the serum concentration of CYP3A4 Substrates.
SimeprevirMay increase the serum concentration of CYP3A4 Substrates.
Sipuleucel-TImmunosuppressants may diminish the therapeutic effect of Sipuleucel-T.
TocilizumabMay decrease the serum concentration of CYP3A4 Substrates.
TofacitinibImmunosuppressants may enhance the immunosuppressive effect of Tofacitinib.
TrastuzumabMay enhance the neutropenic effect of Immunosuppressants.
VincristineTeniposide may enhance the neurotoxic effect of VinCRIStine.
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 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.

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 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

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

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