Identification

Name
Teniposide
Accession Number
DB00444  (APRD00649)
Type
Small Molecule
Groups
Approved
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
  • Teniposide
  • Téniposide
  • Teniposido
  • Teniposidum
External IDs
EPT / PGT / VM-26 / VM26
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TeniposideInjection, solution10 mg/1mLIntravenousWG Critical Care, LLC2013-04-30Not applicableUs
VumonLiquid10 mgIntravenousBristol Myers Squibb1984-12-31Not applicableCanada
VumonInjection, solution10 mg/1mLIntravenousE.R. Squibb & Sons, L.L.C.1992-07-142015-07-14Us
International/Other Brands
Bang Lai (Double-Crane)
Categories
UNII
957E6438QA
CAS number
29767-20-2
Weight
Average: 656.654
Monoisotopic: 656.1563618
Chemical Formula
C32H32O13S
InChI Key
NRUKOCRGYNPUPR-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

Pharmacology

Indication

Teniposide is used for the treatment of refractory acute lymphoblastic leukaemia

Associated Conditions
Pharmacodynamics

Teniposide 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 action

The 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.

TargetActionsOrganism
ADNA topoisomerase 2-alpha
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Route of elimination

From 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 life

5 hours

Clearance
  • 10.3 mL/min/m2
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Teniposide Action PathwayDrug action
Teniposide Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Teniposide.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Teniposide.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Teniposide is combined with 2-Methoxyethanol.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Teniposide.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Teniposide.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Teniposide.
6-Deoxyerythronolide BThe metabolism of Teniposide can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Teniposide.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Teniposide is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Teniposide.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D02698
KEGG Compound
C11153
PubChem Compound
452548
PubChem Substance
46507536
ChemSpider
398606
ChEMBL
CHEMBL452231
Therapeutic Targets Database
DAP000651
PharmGKB
PA451611
HET
9TP
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Teniposide
ATC Codes
L01CB02 — Teniposide
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
4l9q
MSDS
Download (46.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic1
2CompletedTreatmentMalignant Lymphomas1
2RecruitingTreatmentRecurrent B-Cell Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood B-Lymphoblastic Lymphoma1
2Unknown StatusTreatmentLeukemias1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
4Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
4CompletedTreatmentAdult Acute Lymphocytic Leukemia4
4Unknown StatusTreatmentAdult Acute Lymphocytic Leukemia1
Not AvailableCompletedTreatmentBipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1
Not AvailableUnknown StatusTreatmentLeukemias1

Pharmacoeconomics

Manufacturers
  • Bristol myers squibb co pharmaceutical research institute
Packagers
  • Bristol-Myers Squibb Co.
  • Mead Johnson and Co.
Dosage forms
FormRouteStrength
Injection, solutionIntravenous10 mg/1mL
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)242-246 °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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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).
Kingdom
Organic compounds
Super Class
Lignans, neolignans and related compounds
Class
Lignan lactones
Sub Class
Podophyllotoxins
Direct Parent
Podophyllotoxins
Alternative Parents
Aryltetralin lignans / Furanonaphthodioxoles / Tetralins / Pyranodioxins / Dimethoxybenzenes / Methoxyphenols / Benzodioxoles / Anisoles / Phenoxy compounds / Alkyl aryl ethers
show 16 more
Substituents
Podophyllotoxin / 1-aryltetralin lignan / Linear furanonaphthodioxole / Naphthofuran / Methoxyphenol / Pyranodioxin / Tetralin / M-dimethoxybenzene / Dimethoxybenzene / Benzodioxole
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not 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 segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
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
Inhibitor
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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]
  2. Baumhakel M, Kasel D, Rao-Schymanski RA, Bocker R, Beckurts KT, Zaigler M, Barthold D, Fuhr U: Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes. Int J Clin Pharmacol Ther. 2001 Dec;39(12):517-28. [PubMed:11770832]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
There are limited data supporting this interaction, however, the monograph for teniposide indicates that it is a weak inhibitor of CYP2C9.
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Teniposide monograph [File]
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
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]
  2. Relling MV, Nemec J, Schuetz EG, Schuetz JD, Gonzalez FJ, Korzekwa KR: O-demethylation of epipodophyllotoxins is catalyzed by human cytochrome P450 3A4. Mol Pharmacol. 1994 Feb;45(2):352-8. [PubMed:8114683]

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...
Gene Name
ABCC6
Uniprot ID
O95255
Uniprot Name
Multidrug resistance-associated protein 6
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 fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
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]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 03:11