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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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Teniposido [INN-Spanish]
Teniposidum [INN-Latin]
Salts Not Available
Brand names
Name Company
Vee M-26
Veham-Sandoz
Vehem
Vumon
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Nucleic Acid Synthesis Inhibitors
CAS number 29767-20-2
Weight Average: 656.654
Monoisotopic: 656.1563618
Chemical Formula C32H32O13S
InChI Key InChIKey=NRUKOCRGYNPUPR-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Podophyllotoxins
Substructures
  • Podophyllotoxins
  • Carboxylic Acids and Derivatives
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Pyrans
  • Benzyl Alcohols and Derivatives
  • Naphthalenes
  • Acetates
  • Acetals and Derivatives
  • Phenols and Derivatives
  • Lactones
  • Carbohydrates
  • Ethers
  • Benzene and Derivatives
  • Dioxanes
  • Dioxoles
  • Methoxyphenols
  • Catechols
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Aromatic compounds
  • Benzodioxoles
  • Anisoles
  • Furans
  • Cyclohexenes and Derivatives
  • Thiophenes
  • Phenyl Esters
Pharmacology
Indication Teniposide is used for the treatment of refractory acute lymphoblastic leukaemia
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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Not Available
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
Pathway Name SMPDB ID
Smp00443 Teniposide Pathway SMP00443
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb co pharmaceutical research institute
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Prices
Unit description Cost Unit
Vumon 10 mg/ml ampul 75.31 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 242-246 °C PhysProp
logP 1.24 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 5.98e-02 g/l ALOGPS
logP 2.78 ALOGPS
logP 2.78 ChemAxon
logS -4 ALOGPS
pKa (strongest acidic) 9.33 ChemAxon
pKa (strongest basic) -3.7 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 12 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 160.83 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 155.61 ChemAxon
polarizability 65.8 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02698 Link_out
KEGG Compound C11153 Link_out
PubChem Compound 34698 Link_out
PubChem Substance 46507536 Link_out
ChemSpider 31930 Link_out
Therapeutic Targets Database DAP000651 Link_out
PharmGKB PA451611 Link_out
Drug Product Database 588989 Link_out
RxList http://www.rxlist.com/cgi/generic2/teniposide.htm Link_out
Drugs.com http://www.drugs.com/cdi/teniposide.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Teniposide Link_out
ATC Codes
  • L01CB02
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label Not Available
MSDS show (46.6 KB)
Interactions
Drug Interactions
Drug Interaction
Amprenavir The 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.
Atazanavir The 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.
Butabarbital Barbiturates like butabarbital may decrease the serum concentration of Teniposide. arbiturates may decrease the serum concentration of Teniposide.
Butalbital Barbiturates 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.
Clarithromycin The 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.
Conivaptan The 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.
Darunavir The 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.
Delavirdine The 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.
Fosamprenavir The 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.
Imatinib The 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.
Indinavir The 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.
Isoniazid The 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.
Itraconazole The 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.
Ketoconazole The 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.
Lopinavir The 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.
Miconazole The 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.
Natalizumab The immunosuppressant, Teniposide, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
Nefazodone The 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.
Nelfinavir The 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.
Nicardipine The 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.
Posaconazole The 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.
Quinidine The 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.
Quinupristin This combination presents an increased risk of toxicity
Ritonavir The 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.
Saquinavir The 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.
Telithromycin The 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.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Voriconazole The 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 Interactions Not Available
Targets

1. DNA topoisomerase 2-alpha

Pharmacological action: yes
Actions: inhibitor

Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks

Organism class: human
UniProt ID: P11388 Link_out
Gene: TOP2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

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 xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

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, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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)

UniProt ID: O95255 Link_out
Gene: ABCC6 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19