Identification
- Summary
Etoposide is a podophyllotoxin derivative used to treat testicular and small cell lung tumors.
- Brand Names
- Etopophos, Vepesid
- Generic Name
- Etoposide
- DrugBank Accession Number
- DB00773
- Background
A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide 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 entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Etoposide (DB00773)
- Weight
- Average: 588.5566
Monoisotopic: 588.18429111 - Chemical Formula
- C29H32O13
- Synonyms
- (−)-etoposide
- 4-demethylepipodophyllotoxin β-D-ethylideneglucoside
- 4'-Demethylepipodophyllotoxin 9-(4,6-O-(R)-ethylidene-beta-D-glucopyranoside)
- 9-((4,6-O-Ethylidine-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,4-dimethyloxyphenyl)furo(3',4'':6,7)naptho-(2,3-d)-1,3-dioxol-6(5aH)-one
- Etoposide
- Etoposido
- Etoposidum
- trans-Etoposide
- External IDs
- NSC-141540
- VP-16-213
Pharmacology
- Indication
For use in combination with other chemotherapeutic agents in the treatment of refractory testicular tumors and as first line treatment in patients with small cell lung cancer. Also used to treat other malignancies such as lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Acute lymphoblastic leukemia ••• ••••• Treatment of Acute myeloid leukemia ••• ••••• Used in combination to treat Ewing's sarcoma ••• ••••• Treatment of Gestational trophoblastic disease ••• ••••• Treatment of Merkel cell cancer ••• ••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Etoposide is an antineoplastic agent and an epipodophyllotoxin (a semisynthetic derivative of the podophyllotoxins). It inhibits DNA topoisomerase II, thereby ultimately inhibiting DNA synthesis. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases. Two different dose-dependent responses are seen. At high concentrations (10 µg/mL or more), lysis of cells entering mitosis is observed. At low concentrations (0.3 to 10 µg/mL), cells are inhibited from entering prophase. It does not interfere with microtubular assembly. The predominant macromolecular effect of etoposide appears to be the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals.
- Mechanism of action
Etoposide inhibits DNA topoisomerase II, thereby inhibiting DNA re-ligation. This causes critical errors in DNA synthesis at the premitotic stage of cell division and can lead to apoptosis of the cancer cell. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases of cell division. Inhibition of the topoisomerase II alpha isoform results in the anti-tumour activity of etoposide. The drug is also capable of inhibiting the beta isoform but inhibition of this target is not associated with the anti-tumour activity. It is instead associated with the carcinogenic effect.
Target Actions Organism ADNA topoisomerase 2-alpha inhibitorHumans NDNA topoisomerase 2-beta inhibitorHumans - Absorption
Absorbed well, time to peak plasma concentration is 1-1.5 hrs. Mean bioavailability is 50% (range of 25% - 75%). Cmax and AUC values for orally administered etoposide capsules display intra- and inter-subject variability. There is no evidence of first-pass effect for etoposide.
- Volume of distribution
The disposition of etoposide is a biphasic process with a distribution half-life of 1.5 hours. It does not cross into cerebrospinal fluid well. Volume of distribution, steady state = 18 - 29 L.
- Protein binding
97% protein bound.
- Metabolism
Primarily hepatic (through O-demethylation via the CYP450 3A4 isoenzyme pathway) with 40% excreted unchanged in the urine. Etoposide also undergoes glutathione and glucuronide conjugation which are catalyzed by GSTT1/GSTP1 and UGT1A1, respectively. Prostaglandin synthases are also responsible for the conversion of etoposide to O-demethylated metabolites (quinone).
Hover over products below to view reaction partners
- Route of elimination
Etoposide is cleared by both renal and nonrenal processes, i.e., metabolism and biliary excretion. Glucuronide and/or sulfate conjugates of etoposide are also excreted in human urine. Biliary excretion of unchanged drug and/or metabolites is an important route of etoposide elimination as fecal recovery of radioactivity is 44% of the intravenous dose. 56% of the dose was in the urine, 45% of which was excreted as etoposide.
- Half-life
4-11 hours
- Clearance
- Total body clearance = 33 - 48 mL/min [IV administration, adults]
- Mean renal clearance = 7 - 10 mL/min/m^2
- Adverse Effects
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Side effects include alopecia, constipation, diarrhea, nausea and vomiting and secondary malignancies (leukemia).
- Pathways
Pathway Category Etoposide Metabolism Pathway Drug metabolism Etoposide Action Pathway Drug action - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Etoposide can be increased when it is combined with Abametapir. Abatacept The metabolism of Etoposide can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Etoposide. Abemaciclib Abemaciclib may decrease the excretion rate of Etoposide which could result in a higher serum level. Abiraterone The serum concentration of Etoposide can be increased when it is combined with Abiraterone. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of etoposide.
- Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce serum levels of etoposide.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Etoposide phosphate 528XYJ8L1N 117091-64-2 LIQODXNTTZAGID-OCBXBXKTSA-N - International/Other Brands
- Etopofos (Bristol-Myers Squibb) / Lastet (Cancernova) / Nexvep (Bristol-Myers Squibb) / Vepesid K (Bristol-Myers Squibb) / Vépéside (Novartis)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Eposin Liquid 20 mg / mL Intravenous Pharmachemie B.V. Not applicable Not applicable Canada 
Etopophos Injection, powder, lyophilized, for solution 100 mg/1 Intravenous H2-Pharma, LLC 2009-06-01 Not applicable US 
Etopophos Injection, powder, lyophilized, for solution 100 mg/1 Intravenous E.R. Squibb & Sons, L.L.C. 2009-06-01 2021-04-30 US Etoposide Injection 20 mg/1mL Intravenous ThyMoorgan GmbH Pharmazir & Co. K.G 2017-10-23 Not applicable US Etoposide Injection 20 mg/1mL Intravenous Mylan Laboratories Limited 2018-01-03 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Dom-etoposide Liquid 20 mg / mL Intravenous Dominion Pharmacal Not applicable Not applicable Canada Etoposide Capsule 50 mg/1 Oral Mylan Pharmaceuticals Inc. 2001-10-22 Not applicable US Etoposide Injection, solution 20 mg/1mL Intravenous Fresenius Kabi USA, LLC 2001-07-18 Not applicable US Etoposide Injection 20 mg/1mL Intravenous Accord Healthcare Inc. 2013-08-22 2021-10-31 US Etoposide Injection 20 mg/1mL Intravenous Hikma Pharmaceuticals USA Inc. 1996-05-01 Not applicable US
Categories
- ATC Codes
- L01CB01 — Etoposide
- Drug Categories
- Antineoplastic Agents
- Antineoplastic Agents, Phytogenic
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Carbohydrates
- Cardiotoxic antineoplastic agents
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP2E1 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Glucosides
- Glycosides
- Immunosuppressive Agents
- Myelosuppressive Agents
- Naphthalenes
- Narrow Therapeutic Index Drugs
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Podophyllotoxin
- Podophyllotoxin Derivatives
- Tetrahydronaphthalenes
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- UGT1A1 Substrates
- UGT1A1 Substrates with a Narrow Therapeutic Index
- Chemical TaxonomyProvided by Classyfire
- 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 14 more
- Substituents
- 1,2-diol / 1-aryltetralin lignan / Acetal / Alcohol / Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound / Benzenoid / Benzodioxole / Carbonyl group show 30 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- organic heterotetracyclic compound, beta-D-glucoside, furonaphthodioxole (CHEBI:4911)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6PLQ3CP4P3
- CAS number
- 33419-42-0
- InChI Key
- VJJPUSNTGOMMGY-MRVIYFEKSA-N
- InChI
- InChI=1S/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15+,20-,21-,22+,24-,25-,26-,27-,29+/m1/s1
- IUPAC Name
- (10R,11R,15R,16S)-16-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-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-1,3(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@H]2O[C@@H]1O[C@]2([H])CO[C@@H](C)O[C@@]2([H])[C@H](O)[C@H]1O
References
- Synthesis Reference
- US3524844
- General References
- Zhou Z, Zwelling LA, Ganapathi R, Kleinerman ES: Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase IIalpha gene transfer is independent of topoisomerase IIbeta. Br J Cancer. 2001 Sep 1;85(5):747-51. [Article]
- Azarova AM, Lyu YL, Lin CP, Tsai YC, Lau JY, Wang JC, Liu LF: Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11014-9. Epub 2007 Jun 19. [Article]
- External Links
- Human Metabolome Database
- HMDB0014911
- KEGG Drug
- D00125
- KEGG Compound
- C01576
- PubChem Compound
- 36462
- PubChem Substance
- 46505434
- ChemSpider
- 33510
- BindingDB
- 50127140
- 4179
- ChEBI
- 4911
- ChEMBL
- CHEMBL44657
- ZINC
- ZINC000003938684
- Therapeutic Targets Database
- DAP000786
- PharmGKB
- PA449552
- PDBe Ligand
- EVP
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Etoposide
- PDB Entries
- 3qx3 / 4lb9 / 5cdn / 5cdp / 5gwk / 5zrf / 6zy5 / 6zy6 / 6zy7 / 6zy8 … show 1 more
- FDA label
- Download (206 KB)
- MSDS
- Download (24.1 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Central Nervous System Embryonal Tumors / Medulloblastomas 1 4 Completed Treatment Acute Lymphobkastic Leukemia 1 4 Completed Treatment Acute Lymphoblastic Leukaemias (ALL) 1 4 Completed Treatment Extensive-stage Small Cell Lung Cancer (SCLC) 1 4 Completed Treatment Leukemia, Lymphocytic, Acute, Adult 1
Pharmacoeconomics
- Manufacturers
- Mylan pharmaceuticals inc
- Bristol myers squibb co
- Accord healthcare inc usa
- App pharmaceuticals llc
- Bedford laboratories div ben venue laboratories inc
- Hospira inc
- Marsam pharmaceuticals llc
- Pharmachemie bv
- Pierre fabre medicament
- Teva parenteral medicines inc
- Watson laboratories inc
- Packagers
- APP Pharmaceuticals
- Baxter International Inc.
- Bedford Labs
- Ben Venue Laboratories Inc.
- Bristol-Myers Squibb Co.
- Hospira Inc.
- Mead Johnson and Co.
- Mylan
- Pfizer Inc.
- Pharmachemie BV
- Pharmacia Inc.
- R.P. Scherer GmbH and Co. KG
- RP Scherer Canada Inc.
- Sicor Pharmaceuticals
- Teva Pharmaceutical Industries Ltd.
- UDL Laboratories
- Wyeth Pharmaceuticals
- Dosage Forms
Form Route Strength Solution Intravenous 20.000 mg Solution Parenteral 100 mg Injection, solution, concentrate Intravenous 20.00 mg Solution, concentrate Intravenous 20 mg Injection, solution, concentrate Intravenous 1000 mg/50ml Injection, solution, concentrate Intravenous 200 mg/10ml Injection, solution, concentrate Intravenous 500 mg/25ml Injection, powder, lyophilized, for solution Intravenous 100 mg/1 Powder, for solution Injection, solution, concentrate Intravenous 50 mg/2.5ml Capsule Oral 50 mg/1 Injection Intravenous 20 mg/1mL Injection, solution Intravenous 20 mg/1mL Injection, solution, concentrate Intravenous Injection, solution, concentrate Intravenous 20 mg/ml Liquid Intravenous 20 mg / mL Solution Intravenous 20 mg / mL Injection, solution, concentrate Intravenous; Parenteral 20 MG/ML Solution 100 mg/5ml Injection Intravenous 20 mg/ml Injection Parenteral 100 mg Injection Intravenous 100 mg Solution Intravenous 0.1 g Solution Parenteral 20 mg Solution, concentrate Parenteral 100 mg Solution Parenteral 50 mg Solution Parenteral 0.1 g Solution Intravenous 100 mg Solution Intravenous 20 mg Injection Intravenous Solution Intravenous 100 mg/5ml Solution Intravenous 50 mg/2.5ml Solution Intravenous 100.000 mg Injection, solution Intravenous 20 MG/ML Capsule Oral Injection, solution Intravenous Injection, solution Intravenous 100 mg Capsule Oral 25 mg Solution Intravenous 100.0 mg Injection, solution, concentrate Intravenous 100 mg/5ml Solution Parenteral Injection, solution, concentrate Intravenous 20 mg/1mL Capsule Oral 100 MG Capsule, liquid filled Oral 50 mg/1 Injection Intravenous 1 g/50mL Injection Intravenous 100 mg/5mL Injection Intravenous 150 mg/7.5mL Injection Intravenous 500 mg/25mL Injection, solution Intravenous 100 MG/5ML Capsule, coated Oral 50 mg Capsule Oral 50 mg Solution 20 mg/1ml - Prices
Unit description Cost Unit VePesid 20 50 mg capsule Box 1273.41USD box Etopophos 100 mg vial 159.55USD vial Etoposide 50 mg capsule 47.64USD capsule Etoposide 100 mg/5 ml vial 28.89USD ml Toposar 100 mg/5 ml vial 2.25USD ml Toposar 1000 mg/50 ml vial 1.12USD ml Toposar 500 mg/25 ml vial 1.06USD 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) 236-251 °C PhysProp water solubility Sparingly soluble FDA label logP 0.60 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.978 mg/mL ALOGPS logP 0.73 ALOGPS logP 1.16 Chemaxon logS -2.8 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 5 Chemaxon Refractivity 139.02 m3·mol-1 Chemaxon Polarizability 57.95 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.836 Blood Brain Barrier - 0.9609 Caco-2 permeable - 0.5234 P-glycoprotein substrate Substrate 0.7019 P-glycoprotein inhibitor I Non-inhibitor 0.8005 P-glycoprotein inhibitor II Non-inhibitor 0.8381 Renal organic cation transporter Non-inhibitor 0.8412 CYP450 2C9 substrate Non-substrate 0.8228 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.6134 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.6884 CYP450 2D6 inhibitor Non-inhibitor 0.8392 CYP450 2C19 inhibitor Non-inhibitor 0.529 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5576 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.9325 Biodegradation Not ready biodegradable 0.9467 Rat acute toxicity 2.9588 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9847 hERG inhibition (predictor II) Non-inhibitor 0.8734
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 257.0418381 predictedDarkChem Lite v0.1.0 [M-H]- 224.4481 predictedDeepCCS 1.0 (2019) [M+H]+ 257.6473381 predictedDarkChem Lite v0.1.0 [M+H]+ 226.3435 predictedDeepCCS 1.0 (2019) [M+Na]+ 256.7566381 predictedDarkChem Lite v0.1.0 [M+Na]+ 232.12144 predictedDeepCCS 1.0 (2019)
Targets
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- 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. [Article]
- Lopez-Lazaro M, Pastor N, Azrak SS, Ayuso MJ, Austin CA, Cortes F: Digitoxin inhibits the growth of cancer cell lines at concentrations commonly found in cardiac patients. J Nat Prod. 2005 Nov;68(11):1642-5. [Article]
- Moneypenny CG, Shao J, Song Y, Gallagher EP: MLL rearrangements are induced by low doses of etoposide in human fetal hematopoietic stem cells. Carcinogenesis. 2006 Apr;27(4):874-81. Epub 2005 Dec 24. [Article]
- 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. [Article]
- Winnicka K, Bielawski K, Bielawska A: Cardiac glycosides in cancer research and cancer therapy. Acta Pol Pharm. 2006 Mar-Apr;63(2):109-15. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Protein kinase c binding
- Specific Function
- Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
- Gene Name
- TOP2B
- Uniprot ID
- Q02880
- Uniprot Name
- DNA topoisomerase 2-beta
- Molecular Weight
- 183265.825 Da
References
- Azarova AM, Lyu YL, Lin CP, Tsai YC, Lau JY, Wang JC, Liu LF: Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11014-9. Epub 2007 Jun 19. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- 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
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Kawashiro T, Yamashita K, Zhao XJ, Koyama E, Tani M, Chiba K, Ishizaki T: A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther. 1998 Sep;286(3):1294-300. [Article]
- Li X, Yun JK, Choi JS: Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6. doi: 10.1002/bdd.539. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Kawashiro T, Yamashita K, Zhao XJ, Koyama E, Tani M, Chiba K, Ishizaki T: A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther. 1998 Sep;286(3):1294-300. [Article]
- Kind
- Protein
- Organism
- Humans
- 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 un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Zhuo X, Zheng N, Felix CA, Blair IA: Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000. [Article]
- Yang J, Bogni A, Schuetz EG, Ratain M, Dolan ME, McLeod H, Gong L, Thorn C, Relling MV, Klein TE, Altman RB: Etoposide pathway. Pharmacogenet Genomics. 2009 Jul;19(7):552-3. doi: 10.1097/FPC.0b013e32832e0e7f. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
References
- Wen Z, Tallman MN, Ali SY, Smith PC: UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80. Epub 2006 Dec 6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Glutathione transferase activity
- Specific Function
- Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Acts on 1,2-epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4-nitrobenzyl chlorid...
- Gene Name
- GSTT1
- Uniprot ID
- P30711
- Uniprot Name
- Glutathione S-transferase theta-1
- Molecular Weight
- 27334.755 Da
References
- Mans DR, Lafleur MV, Westmijze EJ, Horn IR, Bets D, Schuurhuis GJ, Lankelma J, Retel J: Reactions of glutathione with the catechol, the ortho-quinone and the semi-quinone free radical of etoposide. Consequences for DNA inactivation. Biochem Pharmacol. 1992 Apr 15;43(8):1761-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- S-nitrosoglutathione binding
- Specific Function
- Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
- Gene Name
- GSTP1
- Uniprot ID
- P09211
- Uniprot Name
- Glutathione S-transferase P
- Molecular Weight
- 23355.625 Da
References
- Mans DR, Lafleur MV, Westmijze EJ, Horn IR, Bets D, Schuurhuis GJ, Lankelma J, Retel J: Reactions of glutathione with the catechol, the ortho-quinone and the semi-quinone free radical of etoposide. Consequences for DNA inactivation. Biochem Pharmacol. 1992 Apr 15;43(8):1761-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
References
- Haim N, Roman J, Nemec J, Sinha BK: Peroxidative free radical formation and O-demethylation of etoposide(VP-16) and teniposide(VM-26). Biochem Biophys Res Commun. 1986 Feb 26;135(1):215-20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
- Gene Name
- PTGS1
- Uniprot ID
- P23219
- Uniprot Name
- Prostaglandin G/H synthase 1
- Molecular Weight
- 68685.82 Da
References
- Haim N, Roman J, Nemec J, Sinha BK: Peroxidative free radical formation and O-demethylation of etoposide(VP-16) and teniposide(VM-26). Biochem Biophys Res Commun. 1986 Feb 26;135(1):215-20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- 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
- Kawashiro T, Yamashita K, Zhao XJ, Koyama E, Tani M, Chiba K, Ishizaki T: A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther. 1998 Sep;286(3):1294-300. [Article]
- Schuetz E, Lan L, Yasuda K, Kim R, Kocarek TA, Schuetz J, Strom S: Development of a real-time in vivo transcription assay: application reveals pregnane X receptor-mediated induction of CYP3A4 by cancer chemotherapeutic agents. Mol Pharmacol. 2002 Sep;62(3):439-45. [Article]
- Zhuo X, Zheng N, Felix CA, Blair IA: Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000. [Article]
- Yang J, Bogni A, Schuetz EG, Ratain M, Dolan ME, McLeod H, Gong L, Thorn C, Relling MV, Klein TE, Altman RB: Etoposide pathway. Pharmacogenet Genomics. 2009 Jul;19(7):552-3. doi: 10.1097/FPC.0b013e32832e0e7f. [Article]
- Badowski ME, Burton B, Shaeer KM, Dicristofano J: Oral oncolytic and antiretroviral therapy administration: dose adjustments, drug interactions, and other considerations for clinical use. Drugs Context. 2019 Feb 13;8:212550. doi: 10.7573/dic.212550. eCollection 2019. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Organic anion transmembrane transporter activity
- Specific Function
- May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
- Gene Name
- ABCC3
- Uniprot ID
- O15438
- Uniprot Name
- Canalicular multispecific organic anion transporter 2
- Molecular Weight
- 169341.14 Da
References
- Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [Article]
- Zehnpfennig B, Urbatsch IL, Galla HJ: Functional reconstitution of human ABCC3 into proteoliposomes reveals a transport mechanism with positive cooperativity. Biochemistry. 2009 May 26;48(20):4423-30. doi: 10.1021/bi9001908. [Article]
- Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P: Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem. 2001 Dec 7;276(49):46400-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Cai J, Daoud R, Alqawi O, Georges E, Pelletier J, Gros P: Nucleotide binding and nucleotide hydrolysis properties of the ABC transporter MRP6 (ABCC6). Biochemistry. 2002 Jun 25;41(25):8058-67. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. [Article]
- Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [Article]
- Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):765-72. [Article]
- Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [Article]
- Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [Article]
- Guo A, Marinaro W, Hu P, Sinko PJ: Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos. 2002 Apr;30(4):457-63. [Article]
- Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Transporter activity
- Specific Function
- Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
- Gene Name
- ABCC1
- Uniprot ID
- P33527
- Uniprot Name
- Multidrug resistance-associated protein 1
- Molecular Weight
- 171589.5 Da
References
- Heijn M, Hooijberg JH, Scheffer GL, Szabo G, Westerhoff HV, Lankelma J: Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport. Biochim Biophys Acta. 1997 May 22;1326(1):12-22. [Article]
- Guo A, Marinaro W, Hu P, Sinko PJ: Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos. 2002 Apr;30(4):457-63. [Article]
- Godinot N, Iversen PW, Tabas L, Xia X, Williams DC, Dantzig AH, Perry WL 3rd: Cloning and functional characterization of the multidrug resistance-associated protein (MRP1/ABCC1) from the cynomolgus monkey. Mol Cancer Ther. 2003 Mar;2(3):307-16. [Article]
- Nunoya K, Grant CE, Zhang D, Cole SP, Deeley RG: Molecular cloning and pharmacological characterization of rat multidrug resistance protein 1 (mrp1). Drug Metab Dispos. 2003 Aug;31(8):1016-26. [Article]
- Stride BD, Grant CE, Loe DW, Hipfner DR, Cole SP, Deeley RG: Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. Mol Pharmacol. 1997 Sep;52(3):344-53. [Article]
- Wong IL, Chan KF, Tsang KH, Lam CY, Zhao Y, Chan TH, Chow LM: Modulation of multidrug resistance protein 1 (MRP1/ABCC1)-mediated multidrug resistance by bivalent apigenin homodimers and their derivatives. J Med Chem. 2009 Sep 10;52(17):5311-22. doi: 10.1021/jm900194w. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Atpase activity, coupled to transmembrane movement of substances
- Specific Function
- ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
- Gene Name
- ABCC10
- Uniprot ID
- Q5T3U5
- Uniprot Name
- Multidrug resistance-associated protein 7
- Molecular Weight
- 161627.375 Da
References
- Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [Article]
- Hopper-Borge E, Xu X, Shen T, Shi Z, Chen ZS, Kruh GD: Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B. Cancer Res. 2009 Jan 1;69(1):178-84. doi: 10.1158/0008-5472.CAN-08-1420. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Organic anion transmembrane transporter activity
- Specific Function
- Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- Canalicular multispecific organic anion transporter 1
- Molecular Weight
- 174205.64 Da
References
- Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MRP2 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):773-9. [Article]
- Guo A, Marinaro W, Hu P, Sinko PJ: Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos. 2002 Apr;30(4):457-63. [Article]
- 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
- Wang X, Furukawa T, Nitanda T, Okamoto M, Sugimoto Y, Akiyama S, Baba M: Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72. [Article]
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54