Identification

Name
Podofilox
Accession Number
DB01179  (APRD01189, DB08417)
Type
Small Molecule
Groups
Approved
Description

A lignan (lignans) found in podophyllin resin from the roots of podophyllum plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [PubChem]

Structure
Thumb
Synonyms
  • (-)-Podophyllotoxin
  • 9-HYDROXY-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-D][1,3]dioxol-6(5ah)-one
  • Podofilox
  • Podophyllinic acid lactone
  • Podophyllotoxin
  • Podophyllotoxin 7
  • PPT
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CondylineSolution0.5 %TopicalSanofi Aventis1992-12-31Not applicableCanada
CondyloxGel5 mg/gTopicalActavis Pharma Company1997-03-13Not applicableUs
CondyloxSolution5 mg/mLTopicalActavis Pharma Company1990-12-13Not applicableUs
PodofiloxSolution5 mg/mLTopicalPhysicians Total Care, Inc.2010-11-12Not applicableUs
PodofiloxSolution5 mg/mLTopicalActavis Pharma Company1990-12-13Not applicableUs
WartecLiquid5 mgTopicalStiefel Laboratories, Inc.1995-12-312015-04-30Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PodofiloxSolution5 mg/mLTopicalOceanside Pharmaceuticals2010-07-212017-07-31Us
PodofiloxSolution5 mg/mLTopicalPaddock Laboratories, Inc.2002-01-29Not applicableUs
International/Other Brands
Condylox / Podophyllotoxin / Podophyllotoxin 7
Categories
UNII
L36H50F353
CAS number
518-28-5
Weight
Average: 414.4053
Monoisotopic: 414.13146768
Chemical Formula
C22H22O8
InChI Key
YJGVMLPVUAXIQN-XVVDYKMHSA-N
InChI
InChI=1S/C22H22O8/c1-25-16-4-10(5-17(26-2)21(16)27-3)18-11-6-14-15(30-9-29-14)7-12(11)20(23)13-8-28-22(24)19(13)18/h4-7,13,18-20,23H,8-9H2,1-3H3/t13-,18+,19-,20-/m0/s1
IUPAC Name
(10R,11R,15R,16R)-16-hydroxy-10-(3,4,5-trimethoxyphenyl)-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]](C1=CC(OC)=C(OC)C(OC)=C1)C1=CC3=C(OCO3)C=C1[[email protected]@H]2O

Pharmacology

Indication

For treatment of external genital warts (Condyloma acuminatum).

Structured Indications
Pharmacodynamics

Podofilox, also called podophyllotoxin, is a purer and more stable form of podophyllin in which only the biologically active portion of the compound is present. Podofilox is used to remove certain types of warts on the outside skin of the genital areas.

Mechanism of action

The exact mechanism of action is not well understood. It does appear, however, that it and its derivatives may bind and inhibit topoisomerase II during the late S and early G2 stage. The drug may bind and stabilize the temporary break caused by the enzyme. This disrupts the reparation of the break through which the double-stranded DNA passes, and consequently stops DNA unwinding and replication

TargetActionsOrganism
ADNA topoisomerase 2-alpha
inhibitor
Human
ATubulin alpha-4A chain
inhibitor
Human
ATubulin beta chain
inhibitor
Human
Absorption

Topical application of 0.05 mL of 0.5% podofilox solution to external genitalia did not result in detectable serum levels. Applications of 0.1 to 1.5 mL resulted in peak serum levels of 1 to 17 ng/mL one to two hours after application.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

1.0 to 4.5 hours.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Condyloma acuminatum
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe metabolism of Podofilox can be decreased when combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Podofilox.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Podofilox.Experimental
AmiodaroneThe metabolism of Podofilox can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Podofilox can be increased when it is combined with Aprepitant.Approved, Investigational
ArmodafinilThe metabolism of Podofilox can be decreased when combined with Armodafinil.Approved, Investigational
AtazanavirThe metabolism of Podofilox can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Podofilox can be decreased when combined with Atomoxetine.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Podofilox.Approved, Investigational
BoceprevirThe metabolism of Podofilox can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Podofilox can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Podofilox can be decreased when it is combined with Bosentan.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Podofilox.Approved
CarbamazepineThe metabolism of Podofilox can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Podofilox can be increased when it is combined with Ceritinib.Approved
ChloramphenicolThe metabolism of Podofilox can be decreased when combined with Chloramphenicol.Approved, Vet Approved
CholecalciferolThe metabolism of Podofilox can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Podofilox can be decreased when combined with Cimetidine.Approved
CitalopramThe metabolism of Podofilox can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Podofilox can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Podofilox can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Podofilox can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Podofilox can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Podofilox can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Podofilox can be decreased when combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Podofilox.Approved, Investigational
CyclosporineThe metabolism of Podofilox can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Podofilox.Experimental
DabrafenibThe serum concentration of Podofilox can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Podofilox can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Podofilox can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Podofilox can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Podofilox can be decreased when combined with Delavirdine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Podofilox.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Podofilox.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Podofilox.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Podofilox.Approved
DihydroergotamineThe metabolism of Podofilox can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Podofilox can be decreased when combined with Diltiazem.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Podofilox.Approved, Investigational
DoxycyclineThe metabolism of Podofilox can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Podofilox can be decreased when combined with Dronedarone.Approved
EfavirenzThe metabolism of Podofilox can be decreased when combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Podofilox can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Podofilox can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe metabolism of Podofilox can be decreased when combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Podofilox can be decreased when combined with Esomeprazole.Approved, Investigational
EtravirineThe metabolism of Podofilox can be decreased when combined with Etravirine.Approved
FluconazoleThe metabolism of Podofilox can be decreased when combined with Fluconazole.Approved
FluoxetineThe metabolism of Podofilox can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Podofilox can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Podofilox can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Podofilox can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Podofilox can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Podofilox can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe metabolism of Podofilox can be decreased when combined with Gemfibrozil.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Podofilox.Experimental
IdelalisibThe serum concentration of Podofilox can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Podofilox can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Podofilox can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Podofilox can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Podofilox can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Podofilox can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Podofilox can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Podofilox can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Podofilox can be decreased when combined with Ketoconazole.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Podofilox.Experimental
LobeglitazoneThe metabolism of Podofilox can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe metabolism of Podofilox can be decreased when combined with Lopinavir.Approved
LovastatinThe metabolism of Podofilox can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Podofilox can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Podofilox can be decreased when it is combined with Lumacaftor.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Podofilox.Experimental
MifepristoneThe serum concentration of Podofilox can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Podofilox can be decreased when it is combined with Mitotane.Approved
MoclobemideThe metabolism of Podofilox can be decreased when combined with Moclobemide.Approved
ModafinilThe metabolism of Podofilox can be decreased when combined with Modafinil.Approved, Investigational
NefazodoneThe metabolism of Podofilox can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Podofilox can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Podofilox can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Podofilox can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Podofilox can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Podofilox can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Podofilox can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Podofilox.Experimental, Investigational
OmeprazoleThe metabolism of Podofilox can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Podofilox can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Podofilox.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Podofilox.Approved, Vet Approved
PalbociclibThe serum concentration of Podofilox can be increased when it is combined with Palbociclib.Approved
PantoprazoleThe metabolism of Podofilox can be decreased when combined with Pantoprazole.Approved
PentobarbitalThe metabolism of Podofilox can be increased when combined with Pentobarbital.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Podofilox.Experimental
PhenobarbitalThe metabolism of Podofilox can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Podofilox can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Podofilox can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Podofilox can be increased when combined with Primidone.Approved, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Podofilox.Experimental
RanolazineThe metabolism of Podofilox can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Podofilox can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Podofilox can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Podofilox can be increased when combined with Rifapentine.Approved
SaquinavirThe metabolism of Podofilox can be decreased when combined with Saquinavir.Approved, Investigational
SertralineThe metabolism of Podofilox can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Podofilox can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Podofilox can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Podofilox can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Podofilox can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Podofilox can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Podofilox can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Podofilox can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Podofilox can be decreased when combined with Telithromycin.Approved
TiclopidineThe metabolism of Podofilox can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Podofilox can be decreased when it is combined with Tocilizumab.Approved
TopiramateThe metabolism of Podofilox can be decreased when combined with Topiramate.Approved
TranylcypromineThe metabolism of Podofilox can be decreased when combined with Tranylcypromine.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Podofilox.Approved, Investigational
VenlafaxineThe metabolism of Podofilox can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Podofilox can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Podofilox can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Podofilox can be decreased when combined with Ziprasidone.Approved
ZucapsaicinThe metabolism of Podofilox can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15310
KEGG Compound
C10874
PubChem Compound
10607
PubChem Substance
46505716
ChemSpider
10162
BindingDB
50035218
ChEBI
50305
ChEMBL
CHEMBL61
Therapeutic Targets Database
DNC001139
PharmGKB
PA450993
HET
POD
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Podofilox
ATC Codes
D06BB04 — Podophyllotoxin
AHFS Codes
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
PDB Entries
1sa1
MSDS
Download (55.9 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
SolutionTopical0.5 %
GelTopical5 mg/g
SolutionTopical5 mg/mL
LiquidTopical5 mg
Prices
Unit descriptionCostUnit
Podofilox 0.5% Solution 3.5ml Bottle105.99USD bottle
Condylox 0.5% gel97.73USD g
Wartec 0.5 % Solution14.26USD solution
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)228 °CPhysProp
water solubility100 mg/L (at 25 °C)MERCK INDEX (1996)
logP1.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.114 mg/mLALOGPS
logP2.37ALOGPS
logP1.62ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)14.02ChemAxon
pKa (Strongest Basic)-3.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area92.68 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity103.9 m3·mol-1ChemAxon
Polarizability41.71 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9939
Blood Brain Barrier-0.5388
Caco-2 permeable+0.849
P-glycoprotein substrateNon-substrate0.5382
P-glycoprotein inhibitor IInhibitor0.5455
P-glycoprotein inhibitor IIInhibitor0.6709
Renal organic cation transporterNon-inhibitor0.8403
CYP450 2C9 substrateNon-substrate0.8241
CYP450 2D6 substrateNon-substrate0.8911
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorInhibitor0.8948
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7468
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.91
BiodegradationNot ready biodegradable0.8596
Rat acute toxicity3.0013 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9871
hERG inhibition (predictor II)Non-inhibitor0.9081
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-014i-0932100000-95e1178f6bbdd050862b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTOF , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0597000000-db51a944dfa407960e8d
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000j-0963000000-4476c6936a37aa211aa3
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00ks-2963000000-b25b106b59de4143117b
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0985000000-53e98e579f100740f337
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01q9-0294000000-a3c5accc0b01026c8804
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0986000000-0ae140ecf023e899576f

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 / Benzodioxoles / Phenoxy compounds / Anisoles / Methoxybenzenes / Alkyl aryl ethers / Gamma butyrolactones / Tetrahydrofurans
show 8 more
Substituents
Podophyllotoxin / 1-aryltetralin lignan / Linear furanonaphthodioxole / Naphthofuran / Tetralin / Benzodioxole / Phenoxy compound / Phenol ether / Anisole / Methoxybenzene
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
lignan, furonaphthodioxole (CHEBI:50305) / Phenylpropanoids, Lignans, Phytotoxins (C10874)

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
  1. Iida A, Kano M, Kubota Y, Koga K, Tomioka K: Podophyllotoxin aza-analogue, a novel DNA topoisomerase II inhibitor. Chem Pharm Bull (Tokyo). 2000 Apr;48(4):486-9. [PubMed:10783066]
  2. Zhang YL, Shen YC, Wang ZQ, Chen HX, Guo X, Cheng YC, Lee KH: Antitumor agents, 130, Novel 4 beta-arylamino derivatives of 3',4'-didemethoxy-3',4'-dioxo-4-deoxypodophyllotoxin as potent inhibitors of human DNA topoisomerase II. J Nat Prod. 1992 Aug;55(8):1100-11. [PubMed:1331331]
  3. Terada T, Fujimoto K, Nomura M, Yamashita J, Kobunai T, Takeda S, Wierzba K, Yamada Y, Yamaguchi H: Antitumor agents. I. DNA topoisomerase II inhibitory activity and the structural relationship of podophyllotoxin derivatives as antitumor agents. Chem Pharm Bull (Tokyo). 1992 Oct;40(10):2720-7. [PubMed:1334447]
  4. Kamal A, Gayatri NL, Reddy DR, Mohan Reddy PS, Arifuddin M, Dastidar SG, Kondapi AK, Rajkumar M: Synthesis and biological evaluation of new 4beta-anilino- and 4beta-imido-substituted podophyllotoxin congeners. Bioorg Med Chem. 2005 Nov 15;13(22):6218-25. Epub 2005 Aug 2. [PubMed:16061385]
  5. Ruckdeschel JC: Etoposide in the management of non-small cell lung cancer. Cancer. 1991 Jan 1;67(1 Suppl):250-3. [PubMed:1845848]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Structural constituent of cytoskeleton
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBA4A
Uniprot ID
P68366
Uniprot Name
Tubulin alpha-4A chain
Molecular Weight
49923.995 Da
References
  1. Labruere R, Gautier B, Testud M, Seguin J, Lenoir C, Desbene-Finck S, Helissey P, Garbay C, Chabot GG, Vidal M, Giorgi-Renault S: Design, synthesis, and biological evaluation of the first podophyllotoxin analogues as potential vascular-disrupting agents. ChemMedChem. 2010 Dec 3;5(12):2016-25. doi: 10.1002/cmdc.201000305. [PubMed:20979080]
  2. Li CM, Lu Y, Ahn S, Narayanan R, Miller DD, Dalton JT: Competitive mass spectrometry binding assay for characterization of three binding sites of tubulin. J Mass Spectrom. 2010 Oct;45(10):1160-6. doi: 10.1002/jms.1804. [PubMed:20814887]
  3. Kim ND, Park ES, Kim YH, Moon SK, Lee SS, Ahn SK, Yu DY, No KT, Kim KH: Structure-based virtual screening of novel tubulin inhibitors and their characterization as anti-mitotic agents. Bioorg Med Chem. 2010 Oct 1;18(19):7092-100. doi: 10.1016/j.bmc.2010.07.072. Epub 2010 Aug 6. [PubMed:20810285]
  4. Screpanti E, Santaguida S, Nguyen T, Silvestri R, Gussio R, Musacchio A, Hamel E, De Wulf P: A screen for kinetochore-microtubule interaction inhibitors identifies novel antitubulin compounds. PLoS One. 2010 Jul 15;5(7):e11603. doi: 10.1371/journal.pone.0011603. [PubMed:20657644]
  5. Alam MA, Naik PK: Applying linear interaction energy method for binding affinity calculations of podophyllotoxin analogues with tubulin using continuum solvent model and prediction of cytotoxic activity. J Mol Graph Model. 2009 Jun-Jul;27(8):930-43. doi: 10.1016/j.jmgm.2009.02.003. Epub 2009 Feb 20. [PubMed:19286405]
  6. Clark PI: Clinical pharmacology and schedule dependency of the podophyllotoxin derivatives. Semin Oncol. 1992 Apr;19(2 Suppl 6):20-7. [PubMed:1411635]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBB
Uniprot ID
P07437
Uniprot Name
Tubulin beta chain
Molecular Weight
49670.515 Da
References
  1. Wolff J, Knipling L, Cahnmann HJ, Palumbo G: Direct photoaffinity labeling of tubulin with colchicine. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2820-4. [PubMed:2011590]

Enzymes

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
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:34