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/1gTopicalAllergan1997-03-13Not applicableUs
CondyloxGel5 mg/1gTopicalOclassen Dermatologics2007-05-03Not applicableUs
CondyloxSolution5 mg/1mLTopicalWatson Laboratories, Inc.2007-03-312007-03-31Us
CondyloxSolution5 mg/1mLTopicalActavis Pharma Company1990-12-13Not applicableUs
CondyloxSolution5 mg/1mLTopicalDPT Laboratories, Ltd.1997-05-222009-09-30Us
CondyloxGel5 mg/1gTopicalActavis Pharma Company1997-03-132018-12-31Us
CondyloxSolution5 mg/1mLTopicalPhysicians Total Care, Inc.1990-12-132010-06-30Us
Condylox (podofilox)Topical Solution 0.5%Solution5 mg/1mLTopicalDPT Laboratories, Ltd.2008-07-29Not applicableUs
PodofiloxSolution5 mg/1mLTopicalDPT Laboratories, Ltd.2003-07-302010-01-27Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PodofiloxSolution5 mg/1mLTopicalMetacon Labs2010-07-212014-08-31Us
PodofiloxSolution5 mg/1mLTopicalPhysicians Total Care, Inc.2010-11-12Not applicableUs
PodofiloxSolution5 mg/1mLTopicalActavis Pharma, Inc.1990-12-13Not applicableUs
PodofiloxSolution5 mg/1mLTopicalPaddock Laboratories, Inc.2002-01-29Not applicableUs
PodofiloxSolution5 mg/1mLTopicalOceanside Pharmaceuticals2010-07-212017-07-31Us
PodofiloxGel5 mg/1gTopicalWatson Pharmaceuticals2010-02-012010-02-12Us
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][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

Pharmacology

Indication

For treatment of external genital warts (Condyloma acuminatum).

Associated Conditions
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
DrugInteraction
AmiodaroneThe metabolism of Podofilox can be decreased when combined with Amiodarone.
AmprenavirThe metabolism of Podofilox can be decreased when combined with Amprenavir.
ApalutamideThe serum concentration of Podofilox can be decreased when it is combined with Apalutamide.
AtazanavirThe metabolism of Podofilox can be decreased when combined with Atazanavir.
BoceprevirThe metabolism of Podofilox can be decreased when combined with Boceprevir.
CarbamazepineThe metabolism of Podofilox can be increased when combined with Carbamazepine.
CeritinibThe serum concentration of Podofilox can be increased when it is combined with Ceritinib.
ClarithromycinThe metabolism of Podofilox can be decreased when combined with Clarithromycin.
ClotrimazoleThe metabolism of Podofilox can be decreased when combined with Clotrimazole.
CobicistatThe metabolism of Podofilox can be decreased when combined with Cobicistat.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015310
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
PhaseStatusPurposeConditionsCount
3RecruitingTreatmentExternal Anogenital Warts1

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
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]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 05:49