Teniposide - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (1)Enzymes (4)Transporters (2)

Targets (1)Enzymes (4)Transporters (2)Biointeractions (8)

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

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

4'-demethylepipodophyllotoxin 9-(4,6-O-(R)-2-thenylidene-beta-D-glucopyranoside)

Epidophyllotoxin

Teniposid

Téniposide

Teniposido

Teniposidum

External IDs

EPT / PGT / VM-26 / VM26

Product Ingredients

Not Available

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Teniposide	Injection, solution	10 mg/mL	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

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Name	Company
Bang Lai	Double-Crane

Brand mixtures

Not Available

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][[email protected]]12COC(=O)[[email protected]]1([H])[[email protected]]([H])(C1=CC(OC)=C(O)C(OC)=C1)C1=CC3=C(OCO3)C=C1[[email protected]@]2([H])O[[email protected]]1([H])O[[email protected]]2([H])CO[[email protected]]([H])(O[[email protected]@]2([H])[[email protected]]([H])(O)[[email protected]@]1([H])O)C1=CC=CS1

Pharmacology

Indication

Teniposide is used for the treatment of refractory acute lymphoblastic leukaemia

Structured Indications

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	Kind	Pharmacological action	Actions	Organism	UniProt ID
DNA topoisomerase 2-alpha	Protein	yes	inhibitor	Human	P11388	details

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Substrate	Enzymes	Product
Teniposide	Cytochrome P450 3A5 Cytochrome P450 3A4	Teniposide catechol derivative	Details
Teniposide catechol derivative	Myeloperoxidase	Teniposide o-quinone derivative	Details

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	SMPDB ID
Teniposide Action Pathway	Drug action	SMP00443
Teniposide Metabolism Pathway	Drug metabolism	SMP00602

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
Abiraterone	The metabolism of Teniposide can be decreased when combined with Abiraterone.	Approved
Acetyldigitoxin	Acetyldigitoxin may decrease the cardiotoxic activities of Teniposide.	Approved
Amiodarone	The metabolism of Teniposide can be decreased when combined with Amiodarone.	Approved, Investigational
Amobarbital	The serum concentration of Teniposide can be decreased when it is combined with Amobarbital.	Approved, Illicit
Aprepitant	The serum concentration of Teniposide can be increased when it is combined with Aprepitant.	Approved, Investigational
Armodafinil	The metabolism of Teniposide can be decreased when combined with Armodafinil.	Approved, Investigational
Atazanavir	The metabolism of Teniposide can be decreased when combined with Atazanavir.	Approved, Investigational
Atomoxetine	The metabolism of Teniposide can be decreased when combined with Atomoxetine.	Approved
Barbexaclone	The serum concentration of Teniposide can be decreased when it is combined with Barbexaclone.	Experimental
Barbital	The serum concentration of Teniposide can be decreased when it is combined with Barbital.	Illicit
BCG vaccine	The therapeutic efficacy of Bcg can be decreased when used in combination with Teniposide.	Investigational
Bevacizumab	Bevacizumab may increase the cardiotoxic activities of Teniposide.	Approved, Investigational
Bexarotene	The serum concentration of Teniposide can be decreased when it is combined with Bexarotene.	Approved, Investigational
Boceprevir	The metabolism of Teniposide can be decreased when combined with Boceprevir.	Withdrawn
Bortezomib	The metabolism of Teniposide can be decreased when combined with Bortezomib.	Approved, Investigational
Bosentan	The serum concentration of Teniposide can be decreased when it is combined with Bosentan.	Approved, Investigational
Cabazitaxel	The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Teniposide.	Approved
Carbamazepine	The metabolism of Teniposide can be increased when combined with Carbamazepine.	Approved, Investigational
Ceritinib	The serum concentration of Teniposide can be increased when it is combined with Ceritinib.	Approved
Chloramphenicol	The metabolism of Teniposide can be decreased when combined with Chloramphenicol.	Approved, Vet Approved
Cholecalciferol	The metabolism of Teniposide can be decreased when combined with Cholecalciferol.	Approved, Nutraceutical
Cimetidine	The metabolism of Teniposide can be decreased when combined with Cimetidine.	Approved
Citalopram	The metabolism of Teniposide can be decreased when combined with Citalopram.	Approved
Clarithromycin	The metabolism of Teniposide can be decreased when combined with Clarithromycin.	Approved
Clemastine	The metabolism of Teniposide can be decreased when combined with Clemastine.	Approved
Clotrimazole	The metabolism of Teniposide can be decreased when combined with Clotrimazole.	Approved, Vet Approved
Clozapine	The risk or severity of adverse effects can be increased when Teniposide is combined with Clozapine.	Approved
Cobicistat	The metabolism of Teniposide can be decreased when combined with Cobicistat.	Approved
Conivaptan	The serum concentration of Teniposide can be increased when it is combined with Conivaptan.	Approved, Investigational
Crizotinib	The metabolism of Teniposide can be decreased when combined with Crizotinib.	Approved
Cyclophosphamide	Cyclophosphamide may increase the cardiotoxic activities of Teniposide.	Approved, Investigational
Cyclosporine	The metabolism of Teniposide can be decreased when combined with Cyclosporine.	Approved, Investigational, Vet Approved
Dabrafenib	The serum concentration of Teniposide can be decreased when it is combined with Dabrafenib.	Approved
Darunavir	The metabolism of Teniposide can be decreased when combined with Darunavir.	Approved
Dasatinib	The serum concentration of Teniposide can be increased when it is combined with Dasatinib.	Approved, Investigational
Deferasirox	The serum concentration of Teniposide can be decreased when it is combined with Deferasirox.	Approved, Investigational
Delavirdine	The metabolism of Teniposide can be decreased when combined with Delavirdine.	Approved
Denosumab	The risk or severity of adverse effects can be increased when Denosumab is combined with Teniposide.	Approved
Deslanoside	Deslanoside may decrease the cardiotoxic activities of Teniposide.	Approved
Dexamethasone	The serum concentration of Teniposide can be decreased when it is combined with Dexamethasone.	Approved, Investigational, Vet Approved
Digitoxin	Digitoxin may decrease the cardiotoxic activities of Teniposide.	Approved
Digoxin	Digoxin may decrease the cardiotoxic activities of Teniposide.	Approved
Dihydroergotamine	The metabolism of Teniposide can be decreased when combined with Dihydroergotamine.	Approved
Diltiazem	The metabolism of Teniposide can be decreased when combined with Diltiazem.	Approved
Docetaxel	The risk or severity of adverse effects can be increased when Docetaxel is combined with Teniposide.	Approved, Investigational
Doxycycline	The metabolism of Teniposide can be decreased when combined with Doxycycline.	Approved, Investigational, Vet Approved
Dronedarone	The metabolism of Teniposide can be decreased when combined with Dronedarone.	Approved
Efavirenz	The serum concentration of Teniposide can be decreased when it is combined with Efavirenz.	Approved, Investigational
Eltrombopag	The serum concentration of Teniposide can be increased when it is combined with Eltrombopag.	Approved
Enzalutamide	The serum concentration of Teniposide can be decreased when it is combined with Enzalutamide.	Approved
Erythromycin	The metabolism of Teniposide can be decreased when combined with Erythromycin.	Approved, Vet Approved
Eslicarbazepine acetate	The serum concentration of Teniposide can be decreased when it is combined with Eslicarbazepine acetate.	Approved
Esomeprazole	The metabolism of Teniposide can be decreased when combined with Esomeprazole.	Approved, Investigational
Etravirine	The serum concentration of Teniposide can be decreased when it is combined with Etravirine.	Approved
Fingolimod	Teniposide may increase the immunosuppressive activities of Fingolimod.	Approved, Investigational
Fluconazole	The metabolism of Teniposide can be decreased when combined with Fluconazole.	Approved
Fluoxetine	The metabolism of Teniposide can be decreased when combined with Fluoxetine.	Approved, Vet Approved
Fluvoxamine	The metabolism of Teniposide can be decreased when combined with Fluvoxamine.	Approved, Investigational
Fosamprenavir	The metabolism of Teniposide can be decreased when combined with Fosamprenavir.	Approved
Fosaprepitant	The serum concentration of Teniposide can be increased when it is combined with Fosaprepitant.	Approved
Fosphenytoin	The serum concentration of Teniposide can be decreased when it is combined with Fosphenytoin.	Approved
Fusidic Acid	The serum concentration of Teniposide can be increased when it is combined with Fusidic Acid.	Approved
G17DT	The risk or severity of adverse effects can be increased when Teniposide is combined with G17DT.	Investigational
Gemfibrozil	The metabolism of Teniposide can be decreased when combined with Gemfibrozil.	Approved
GI-5005	The risk or severity of adverse effects can be increased when Teniposide is combined with GI-5005.	Investigational
Hexobarbital	The serum concentration of Teniposide can be decreased when it is combined with Hexobarbital.	Approved
Idelalisib	The serum concentration of Teniposide can be increased when it is combined with Idelalisib.	Approved
Imatinib	The metabolism of Teniposide can be decreased when combined with Imatinib.	Approved
Indinavir	The metabolism of Teniposide can be decreased when combined with Indinavir.	Approved
INGN 201	The risk or severity of adverse effects can be increased when Teniposide is combined with INGN 201.	Investigational
INGN 225	The risk or severity of adverse effects can be increased when Teniposide is combined with INGN 225.	Investigational
Isavuconazonium	The metabolism of Teniposide can be decreased when combined with Isavuconazonium.	Approved, Investigational
Isoniazid	The metabolism of Teniposide can be decreased when combined with Isoniazid.	Approved
Isradipine	The metabolism of Teniposide can be decreased when combined with Isradipine.	Approved
Itraconazole	The metabolism of Teniposide can be decreased when combined with Itraconazole.	Approved, Investigational
Ivacaftor	The serum concentration of Teniposide can be increased when it is combined with Ivacaftor.	Approved
Ketoconazole	The metabolism of Teniposide can be decreased when combined with Ketoconazole.	Approved, Investigational
Leflunomide	The risk or severity of adverse effects can be increased when Teniposide is combined with Leflunomide.	Approved, Investigational
Lopinavir	The metabolism of Teniposide can be decreased when combined with Lopinavir.	Approved
Lovastatin	The metabolism of Teniposide can be decreased when combined with Lovastatin.	Approved, Investigational
Luliconazole	The serum concentration of Teniposide can be increased when it is combined with Luliconazole.	Approved
Lumacaftor	The serum concentration of Teniposide can be decreased when it is combined with Lumacaftor.	Approved
Metamizole	The risk or severity of adverse effects can be increased when Metamizole is combined with Teniposide.	Withdrawn
Methohexital	The serum concentration of Teniposide can be decreased when it is combined with Methohexital.	Approved
Methylphenobarbital	The serum concentration of Teniposide can be decreased when it is combined with Methylphenobarbital.	Approved
Mifepristone	The serum concentration of Teniposide can be increased when it is combined with Mifepristone.	Approved, Investigational
Mitotane	The serum concentration of Teniposide can be decreased when it is combined with Mitotane.	Approved
Moclobemide	The metabolism of Teniposide can be decreased when combined with Moclobemide.	Approved
Modafinil	The serum concentration of Teniposide can be decreased when it is combined with Modafinil.	Approved, Investigational
Nafcillin	The serum concentration of Teniposide can be decreased when it is combined with Nafcillin.	Approved
Natalizumab	The risk or severity of adverse effects can be increased when Teniposide is combined with Natalizumab.	Approved, Investigational
Nefazodone	The metabolism of Teniposide can be decreased when combined with Nefazodone.	Approved, Withdrawn
Nelfinavir	The metabolism of Teniposide can be decreased when combined with Nelfinavir.	Approved
Netupitant	The serum concentration of Teniposide can be increased when it is combined with Netupitant.	Approved
Nevirapine	The metabolism of Teniposide can be increased when combined with Nevirapine.	Approved
Nicardipine	The metabolism of Teniposide can be decreased when combined with Nicardipine.	Approved
Nilotinib	The metabolism of Teniposide can be decreased when combined with Nilotinib.	Approved, Investigational
Olaparib	The metabolism of Teniposide can be decreased when combined with Olaparib.	Approved
Oleandrin	Anvirzel may decrease the cardiotoxic activities of Teniposide.	Experimental
Omeprazole	The metabolism of Teniposide can be decreased when combined with Omeprazole.	Approved, Investigational, Vet Approved
Osimertinib	The serum concentration of Teniposide can be increased when it is combined with Osimertinib.	Approved
Ouabain	Ouabain may decrease the cardiotoxic activities of Teniposide.	Approved
Paclitaxel	The risk or severity of adverse effects can be increased when Paclitaxel is combined with Teniposide.	Approved, Vet Approved
Palbociclib	The serum concentration of Teniposide can be increased when it is combined with Palbociclib.	Approved
Pantoprazole	The metabolism of Teniposide can be decreased when combined with Pantoprazole.	Approved
Pentobarbital	The serum concentration of Teniposide can be decreased when it is combined with Pentobarbital.	Approved, Vet Approved
Phenobarbital	The serum concentration of Teniposide can be decreased when it is combined with Phenobarbital.	Approved
Phenytoin	The serum concentration of Teniposide can be decreased when it is combined with Phenytoin.	Approved, Vet Approved
Pimecrolimus	The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Teniposide.	Approved, Investigational
Posaconazole	The metabolism of Teniposide can be decreased when combined with Posaconazole.	Approved, Investigational, Vet Approved
Primidone	The serum concentration of Teniposide can be decreased when it is combined with Primidone.	Approved, Vet Approved
Rabies virus inactivated antigen, A	The risk or severity of adverse effects can be increased when Teniposide is combined with Rabies vaccine.	Approved
Rabies virus inactivated antigen, A	The therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Teniposide.	Approved
Ranolazine	The metabolism of Teniposide can be decreased when combined with Ranolazine.	Approved, Investigational
Rifabutin	The metabolism of Teniposide can be increased when combined with Rifabutin.	Approved
Rifampicin	The metabolism of Teniposide can be increased when combined with Rifampicin.	Approved
Rifapentine	The metabolism of Teniposide can be increased when combined with Rifapentine.	Approved
Rindopepimut	The risk or severity of adverse effects can be increased when Teniposide is combined with CDX-110.	Investigational
Ritonavir	The metabolism of Teniposide can be decreased when combined with Ritonavir.	Approved, Investigational
Roflumilast	Roflumilast may increase the immunosuppressive activities of Teniposide.	Approved
Rolapitant	The serum concentration of Teniposide can be increased when it is combined with Rolapitant.	Approved
Saquinavir	The metabolism of Teniposide can be decreased when combined with Saquinavir.	Approved, Investigational
Secobarbital	The serum concentration of Teniposide can be decreased when it is combined with Secobarbital.	Approved, Vet Approved
Sertraline	The metabolism of Teniposide can be decreased when combined with Sertraline.	Approved
Sildenafil	The metabolism of Teniposide can be decreased when combined with Sildenafil.	Approved, Investigational
Siltuximab	The serum concentration of Teniposide can be decreased when it is combined with Siltuximab.	Approved
Simeprevir	The serum concentration of Teniposide can be increased when it is combined with Simeprevir.	Approved
Sipuleucel-T	The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Teniposide.	Approved
SRP 299	The risk or severity of adverse effects can be increased when Teniposide is combined with SRP 299.	Investigational
St. John's Wort	The serum concentration of Teniposide can be decreased when it is combined with St. John's Wort.	Nutraceutical
Stiripentol	The serum concentration of Teniposide can be increased when it is combined with Stiripentol.	Approved
Sulfisoxazole	The metabolism of Teniposide can be decreased when combined with Sulfisoxazole.	Approved, Vet Approved
Tacrolimus	The risk or severity of adverse effects can be increased when Tacrolimus is combined with Teniposide.	Approved, Investigational
Telaprevir	The metabolism of Teniposide can be decreased when combined with Telaprevir.	Withdrawn
Telithromycin	The metabolism of Teniposide can be decreased when combined with Telithromycin.	Approved
Teriflunomide	The serum concentration of Teniposide can be increased when it is combined with Teriflunomide.	Approved
TG4010	The risk or severity of adverse effects can be increased when Teniposide is combined with TG4010.	Investigational
Thiamylal	The serum concentration of Teniposide can be decreased when it is combined with Thiamylal.	Approved, Vet Approved
Thiopental	The serum concentration of Teniposide can be decreased when it is combined with Thiopental.	Approved, Vet Approved
Ticlopidine	The metabolism of Teniposide can be decreased when combined with Ticlopidine.	Approved
Tocilizumab	The serum concentration of Teniposide can be decreased when it is combined with Tocilizumab.	Approved
Tofacitinib	Teniposide may increase the immunosuppressive activities of Tofacitinib.	Approved, Investigational
Topiramate	The metabolism of Teniposide can be decreased when combined with Topiramate.	Approved
Tranylcypromine	The metabolism of Teniposide can be decreased when combined with Tranylcypromine.	Approved
Trastuzumab	Trastuzumab may increase the cardiotoxic activities of Teniposide.	Approved, Investigational
Venlafaxine	The metabolism of Teniposide can be decreased when combined with Venlafaxine.	Approved
Verapamil	The metabolism of Teniposide can be decreased when combined with Verapamil.	Approved
Vincristine	Teniposide may increase the neurotoxic activities of Vincristine.	Approved, Investigational
Voriconazole	The metabolism of Teniposide can be decreased when combined with Voriconazole.	Approved, Investigational
Ziprasidone	The metabolism of Teniposide can be decreased when combined with Ziprasidone.	Approved

Food Interactions

Not Available

References

Synthesis Reference

Not Available

General References

Not Available

External Links

Resource	Link
KEGG Drug	D02698
KEGG Compound	C11153
ChemSpider	398606
ChEMBL	CHEMBL452231
Therapeutic Targets Database	DAP000651
PharmGKB	PA451611
HET	9TP
Drug Product Database	1924
RxList	http://www.rxlist.com/cgi/generic2/teniposide.htm
Drugs.com	http://www.drugs.com/cdi/teniposide.html
Wikipedia	Teniposide

ATC Codes

L01CB02 — Teniposide

AHFS Codes

10:00.00

PDB Entries

Not Available

FDA label

Not Available

MSDS

Download (46.6 KB)

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	Active Not Recruiting	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

Dosage forms

Form	Route	Strength
Injection, solution	Intravenous	10 mg/mL
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 Type	Description	Splash Key
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	Not Available

Taxonomy

Description

This compound belongs to the class of chemical entities 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

Chemical entities

Super Class

Organic compounds

Class

Lignans, neolignans and related compounds

Sub Class

Lignan lactones

Direct Parent

Podophyllotoxins

Alternative Parents

Aryltetralin lignans / Furanonaphthodioxoles / Tetralins / Pyranodioxins / Dimethoxybenzenes / Methoxyphenols / Benzodioxoles / Anisoles / Phenoxy compounds / Alkyl aryl ethers

Substituents

Podophyllotoxin / 1-aryltetralin lignan / Linear furanonaphthodioxole / Naphthofuran / Methoxyphenol / Pyranodioxin / Tetralin / M-dimethoxybenzene / Dimethoxybenzene / Benzodioxole

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Targets

Details

1. DNA topoisomerase 2-alpha

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 segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
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

Details

1. Cytochrome P450 2C19

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 imipramine.
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]

Details

2. Cytochrome P450 2C9

Kind: Protein
Organism: Human
Pharmacological action: unknown
Actions: inhibitor

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 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, phenyto...
Gene Name:: CYP2C9
Uniprot ID:: P11712
Uniprot Name:: Cytochrome P450 2C9
Molecular Weight:: 55627.365 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 ]
Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Details

3. Cytochrome P450 3A4

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
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 ]

Details

4. Cytochrome P450 3A5

Kind: Protein
Organism: Human
Pharmacological action: unknown
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
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 ]

Transporters

Details

1. Multidrug resistance-associated protein 6

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) and N-ethylmaleimide S-glutathione (NEM-GS).Isoform 2: Inhibits TNF-alpha-mediated apoptosis through blocking one or more caspases.
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 ]

Details

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

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 from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
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 September 01, 2017 10:27

Structure for DB00444 (Teniposide)

Targets

References

Enzymes

References

References

References

References

Transporters

References

References