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

Similar Structures

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
Vumon	Injection, solution	10 mg/1mL	Intravenous	E.R. Squibb & Sons, L.L.C.	1992-07-14	2015-07-14
Vumon	Liquid	10 mg	Intravenous	Bristol Myers Squibb	1984-12-31	Not applicable

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.

Target	Actions	Organism
ADNA topoisomerase 2-alpha	inhibitor	Humans

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.
7-ethyl-10-hydroxycamptothecin	The metabolism of 7-ethyl-10-hydroxycamptothecin 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.

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	Active Not Recruiting	Treatment	Recurrent B-Cell Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood B-Lymphoblastic Lymphoma	1
2	Completed	Treatment	Acute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic	1
2	Completed	Treatment	Malignant Lymphomas	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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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

Details1. DNA topoisomerase 2-alpha

Kind: Protein
Organism: Humans
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

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
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

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]

Details2. Cytochrome P450 2C9

Kind: Protein
Organism: Humans
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]

Details3. Cytochrome P450 2C19

Kind: Protein
Organism: Humans
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]

Details4. Cytochrome P450 3A5

Kind: Protein
Organism: Humans
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

Details1. Multidrug resistance-associated protein 6

Kind: Protein
Organism: Humans
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]

Details2. ATP-binding cassette sub-family G member 2

Kind: Protein
Organism: Humans
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 April 19, 2019 19:05

Teniposide

Identification

Structure for Teniposide (DB00444)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

Enzymes

References

References

References

References

Transporters

References

References