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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- 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
Structure for Teniposide (DB00444)
- 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
Name Dosage Strength Route Labeller Marketing Start Marketing End Teniposide Injection, solution 10 mg/1mL Intravenous WG Critical Care, LLC 2013-04-30 Not applicable US 
Vumon Liquid 10 mg Intravenous Bristol Myers Squibb 1984-12-31 Not applicable Canada 
Vumon Injection, solution 10 mg/1mL Intravenous E.R. Squibb & Sons, L.L.C. 1992-07-14 2015-07-14 US - International/Other Brands
- Bang Lai (Double-Crane)
- Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Carbohydrates
- Cardiotoxic antineoplastic agents
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Enzyme Inhibitors
- Glucosides
- Glycosides
- Immunosuppressive Agents
- Myelosuppressive Agents
- Neurotoxic agents
- P-glycoprotein/ABCB1 Substrates
- Podophyllotoxin Derivatives
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- 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.
Target Actions Organism ADNA topoisomerase 2-alpha inhibitorHuman - 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
Pathway Category Teniposide Action Pathway Drug action Teniposide Metabolism Pathway Drug metabolism - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction (R)-warfarin The metabolism of (R)-warfarin can be decreased when combined with Teniposide. (S)-Warfarin The metabolism of (S)-Warfarin can be decreased when combined with Teniposide. 2-Methoxyethanol The risk or severity of adverse effects can be increased when Teniposide is combined with 2-Methoxyethanol. 3,5-diiodothyropropionic acid The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Teniposide. 4-hydroxycoumarin The metabolism of 4-hydroxycoumarin can be decreased when combined with Teniposide. 5-androstenedione The metabolism of 5-androstenedione can be decreased when combined with Teniposide. 6-Deoxyerythronolide B The metabolism of Teniposide can be decreased when combined with 6-Deoxyerythronolide B. 6-O-benzylguanine The metabolism of 6-O-benzylguanine can be decreased when combined with Teniposide. 9-(N-methyl-L-isoleucine)-cyclosporin A The risk or severity of adverse effects can be increased when Teniposide is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A. 9-aminocamptothecin The 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
Phase Status Purpose Conditions Count 1, 2 Completed Treatment Malignant Lymphomas 1 2 Completed Treatment Acute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic 1 2 Completed Treatment Malignant Lymphomas 1 2 Recruiting Treatment Recurrent B-Cell Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood B-Lymphoblastic Lymphoma 1 2 Unknown Status Treatment Leukemias 1 3 Completed Treatment Acute Lymphoblastic Leukaemias (ALL) 1 4 Active Not Recruiting Treatment Acute Lymphoblastic Leukaemias (ALL) 1 4 Completed Treatment Adult Acute Lymphocytic Leukemia 4 4 Unknown Status Treatment Adult Acute Lymphocytic Leukemia 1 Not Available Completed Treatment Bipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder 1 Not Available Unknown Status Treatment Leukemias 1
Pharmacoeconomics
- Manufacturers
- Bristol myers squibb co pharmaceutical research institute
- Packagers
- Bristol-Myers Squibb Co.
- Mead Johnson and Co.
- Dosage forms
Form Route Strength Injection, solution Intravenous 10 mg/1mL Liquid Intravenous 10 mg - Prices
Unit description Cost Unit Vumon 10 mg/ml ampul 75.31USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 242-246 °C PhysProp logP 1.24 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.0598 mg/mL 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 Å2 ChemAxon Rotatable Bond Count 6 ChemAxon Refractivity 155.61 m3·mol-1 ChemAxon Polarizability 64.84 Å3 ChemAxon Number of Rings 8 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - 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 inhibitor Non-inhibitor 0.5445 CYP450 2D6 inhibitor Non-inhibitor 0.7197 CYP450 2C19 inhibitor Inhibitor 0.7423 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not 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
- 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]
- 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]
- 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]
- Faure P, Madelaine I: [Topoisomerases: therapeutic value]. Ann Pharm Fr. 1996;54(1):40-4. [PubMed:8702194]
- 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]
- 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
- 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 react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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]
- 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
- 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
- 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
- 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]
- 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
- 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
- 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