Podofilox

Identification

Summary

Podofilox is a topical agent used for the treatment of external genital warts and perianal warts.

Brand Names
Condylox
Generic Name
Podofilox
DrugBank Accession Number
DB01179
Background

A lignan 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.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 414.4053
Monoisotopic: 414.13146768
Chemical Formula
C22H22O8
Synonyms
  • (−)-podophyllotoxin
  • Podofilox
  • Podophyllinic acid lactone
  • Podophyllotoxin
  • PPT

Pharmacology

Indication

For treatment of external genital warts (Condyloma acuminatum).

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofExternal genital warts•••••••••••••••• ••••••••
Treatment ofPerianal warts•••••••••••••••
Treatment ofPerianal warts•••••••••••••••
Contraindications & Blackbox Warnings
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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-beta
modulator
Humans
ATubulin alpha-4A chain
inhibitor
Humans
ATubulin beta chain
inhibitor
Humans
ADNA topoisomerase 2-alpha
inhibitor
Humans
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

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
No interactions found.
Food Interactions
No interactions found.

Products

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International/Other Brands
Podophyllotoxin 7
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CondylineSolution0.5 %TopicalSanofi Aventis Deutschland Gmb H1992-12-312021-08-25Canada flag
CondyloxSolution5 mg/1mLTopicalWatson Labs2007-03-312007-03-31US flag
CondyloxGel5 mg/1gTopicalOclassen Dermatologics2007-05-032007-09-14US flag
CondyloxSolution5 mg/1mLTopicalActavis Pharma, Inc.1990-12-132018-02-28US flag
CondyloxGel5 mg/1gTopicalActavis Pharma Company1997-03-132018-12-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PodofiloxSolution5 mg/1mLTopicalbryant ranch prepack1990-12-13Not applicableUS flag
PodofiloxSolution5 mg/1mLTopicalOceanside Pharmaceuticals2010-07-212017-07-31US flag
PodofiloxSolution5 mg/1mLTopicalPhysicians Total Care, Inc.2010-11-12Not applicableUS flag
PodofiloxSolution5 mg/1mLTopicalPadagis US LLC2002-01-29Not applicableUS flag
PodofiloxSolution5 mg/1mLTopicalMetacon Labs2010-07-212014-08-31US flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
WARTEC CREAM 0.15% w/wCream0.15 % w/wTopicalGlaxosmithkline Consumer Healthcare Ulc2001-07-16Not applicableSingapore flag
WARTEC SOLUTION 0.5% w/vSolution0.5 % w/vTopicalGlaxosmithkline Consumer Healthcare Ulc2001-07-16Not applicableSingapore flag

Categories

ATC Codes
D06BB04 — Podophyllotoxin
Drug Categories
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 / Benzodioxoles / Phenoxy compounds / Anisoles / Methoxybenzenes / Alkyl aryl ethers / Gamma butyrolactones / Tetrahydrofurans
show 8 more
Substituents
1-aryltetralin lignan / Acetal / Alcohol / Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound / Benzenoid / Benzodioxole / Carbonyl group / Carboxylic acid derivative
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
lignan, furonaphthodioxole (CHEBI:50305) / Phenylpropanoids, Lignans, Phytotoxins (C10874)
Affected organisms
  • Condyloma acuminatum

Chemical Identifiers

UNII
L36H50F353
CAS number
518-28-5
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[7.7.0.0^{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(OC)C(OC)=C1)C1=CC3=C(OCO3)C=C1[C@@H]2O

References

General References
Not Available
Human Metabolome Database
HMDB0015310
KEGG Compound
C10874
PubChem Compound
10607
PubChem Substance
46505716
ChemSpider
10162
BindingDB
50035218
RxNav
8463
ChEBI
50305
ChEMBL
CHEMBL61
ZINC
ZINC000003861806
Therapeutic Targets Database
DNC001139
PharmGKB
PA450993
PDBe Ligand
POD
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Podophyllotoxin
PDB Entries
1sa1
MSDS
Download (55.9 KB)

Clinical Trials

Clinical Trials
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
3CompletedTreatmentExternal Anogenital Warts1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • DPT Laboratories Ltd.
  • Oclassen Pharmaceuticals Inc.
  • Paddock Labs
  • Physicians Total Care Inc.
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
SolutionTopical0.5 %
GelTopical5 mg/1g
SolutionTopical5 mg/1mL
SolutionTopical0.5 g
GelTopical0.5 g
CreamTopical
LiquidTopical5 mg / mL
SolutionTopical
CreamTopical0.15 g
SolutionTopical5 mg
CreamTopical0.15 % w/w
SolutionTopical0.5 % w/v
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
Polarizability41.78 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-MSsplash10-0040-1109000000-946a81564d6a1db98613
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-014i-0932100000-95e1178f6bbdd050862b
LC-MS/MS Spectrum - LC-ESI-qTOF , PositiveLC-MS/MSsplash10-000j-0963000000-4476c6936a37aa211aa3
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0002-0597000000-db51a944dfa407960e8d
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-00ks-2963000000-b25b106b59de4143117b
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
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0041900000-ed1b1cf68ab413899f73
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0000900000-724bb4bce95c336ce594
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014j-0029400000-4ebfd5f3c13239e7c4f7
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03e9-0009500000-61f127dd39866946acc9
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-002b-0049000000-5fa802c51ee032cf638c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0f89-0192000000-e056abd91da230bcab2b
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-209.6356744
predicted
DarkChem Lite v0.1.0
[M-H]-213.1269744
predicted
DarkChem Lite v0.1.0
[M-H]-210.6550744
predicted
DarkChem Lite v0.1.0
[M-H]-188.72331
predicted
DeepCCS 1.0 (2019)
[M+H]+209.8348744
predicted
DarkChem Lite v0.1.0
[M+H]+213.3609744
predicted
DarkChem Lite v0.1.0
[M+H]+211.5788744
predicted
DarkChem Lite v0.1.0
[M+H]+191.11888
predicted
DeepCCS 1.0 (2019)
[M+Na]+209.9266744
predicted
DarkChem Lite v0.1.0
[M+Na]+212.8249744
predicted
DarkChem Lite v0.1.0
[M+Na]+210.7155744
predicted
DarkChem Lite v0.1.0
[M+Na]+197.0314
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Modulator
General Function
Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. Plays a role in B-cell differentiation
Specific Function
ATP binding
Gene Name
TOP2B
Uniprot ID
Q02880
Uniprot Name
DNA topoisomerase 2-beta
Molecular Weight
183265.825 Da
References
  1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin
Specific Function
GTP binding
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. Clark PI: Clinical pharmacology and schedule dependency of the podophyllotoxin derivatives. Semin Oncol. 1992 Apr;19(2 Suppl 6):20-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin
Specific Function
GTP binding
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (PubMed:17567603, PubMed:18790802, PubMed:22013166, PubMed:22323612). May play a role in regulating the period length of BMAL1 transcriptional oscillation (By similarity)
Specific Function
ATP binding
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Ruckdeschel JC: Etoposide in the management of non-small cell lung cancer. Cancer. 1991 Jan 1;67(1 Suppl):250-3. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 13, 2024 00:22