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Identification
NamePodofilox
Accession NumberDB01179  (APRD01189, DB08417)
Typesmall molecule
Groupsapproved
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
SynonymLanguageCode
Podophyllinic acid lactoneNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
PodophyllotoxinNot Available
Podophyllotoxin 7Not Available
Brand mixturesNot Available
Categories
CAS number477-47-4
WeightAverage: 414.4053
Monoisotopic: 414.13146768
Chemical FormulaC22H22O8
InChI KeyInChIKey=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(9),2,7-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLignans and Norlignans
ClassLignan Lactones
SubclassPodophyllotoxins
Direct parentPodophyllotoxins
Alternative parentsArylnaphthalene Lignans; Tetralin Lignans; Tetralins; Benzodioxoles; Anisoles; Alkyl Aryl Ethers; Tetrahydrofurans; Oxolanes; Lactones; Carboxylic Acid Esters; Secondary Alcohols; Polyamines; Acetals
Substituentsarylnaphthalene lignan skeleton; tetralin lignan skeleton; tetralin; benzodioxole; phenol ether; anisole; alkyl aryl ether; gamma butyrolactone; benzene; oxolane; tetrahydrofuran; lactone; carboxylic acid ester; secondary alcohol; polyamine; ether; acetal; carboxylic acid derivative; alcohol
Classification descriptionThis compound belongs to the 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).
Pharmacology
IndicationFor treatment of external genital warts (Condyloma acuminatum).
PharmacodynamicsPodofilox, 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 actionThe 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
AbsorptionTopical 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 distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life1.0 to 4.5 hours.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Condyloma acuminatum
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9939
Blood Brain Barrier - 0.5388
Caco-2 permeable + 0.849
P-glycoprotein substrate Non-substrate 0.5382
P-glycoprotein inhibitor I Inhibitor 0.5455
P-glycoprotein inhibitor II Inhibitor 0.6709
Renal organic cation transporter Non-inhibitor 0.8403
CYP450 2C9 substrate Non-substrate 0.8241
CYP450 2D6 substrate Non-substrate 0.8911
CYP450 3A4 substrate Non-substrate 0.5
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Inhibitor 0.8948
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate Inhibitor 0.7959
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7468
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.91
Biodegradation Not ready biodegradable 0.8596
Rat acute toxicity 3.0013 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9871
hERG inhibition (predictor II) Non-inhibitor 0.9081
Pharmacoeconomics
Manufacturers
  • Watson pharmaceuticals inc
  • Collegium pharmaceutical inc
  • Paddock laboratories inc
Packagers
Dosage forms
FormRouteStrength
LiquidTopical
Prices
Unit descriptionCostUnit
Podofilox 0.5% Solution 3.5ml Bottle105.99USDbottle
Condylox 0.5% gel97.73USDg
Wartec 0.5 % Solution14.26USDsolution
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point228 °CPhysProp
water solubility100 mg/L (at 25 °C)MERCK INDEX (1996)
logP1.5Not Available
Predicted Properties
PropertyValueSource
water solubility1.14e-01 g/lALOGPS
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 area92.68ChemAxon
rotatable bond count4ChemAxon
refractivity103.91ChemAxon
polarizability41.71ChemAxon
number of rings5ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC10871
PubChem Compound10607
PubChem Substance46505716
ChemSpider10162
ChEBI50305
ChEMBLCHEMBL61
Therapeutic Targets DatabaseDNC001139
PharmGKBPA450993
HETPOD
RxListhttp://www.rxlist.com/cgi/generic4/podophyllin.htm
Drugs.comhttp://www.drugs.com/cdi/podofilox-gel.html
WikipediaPodofilox
ATC CodesD06BB04
AHFS Codes
  • 84:92.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(55.9 KB)
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

1. DNA topoisomerase 2-alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA topoisomerase 2-alpha P11388 Details

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
  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
  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
  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
  5. Ruckdeschel JC: Etoposide in the management of non-small cell lung cancer. Cancer. 1991 Jan 1;67(1 Suppl):250-3. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Tubulin alpha-4A chain

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Tubulin alpha-4A chain P68366 Details

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. Pubmed
  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. Pubmed
  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. Epub 2010 Aug 6. Pubmed
  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. Pubmed
  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. Epub 2009 Feb 20. Pubmed
  6. Clark PI: Clinical pharmacology and schedule dependency of the podophyllotoxin derivatives. Semin Oncol. 1992 Apr;19(2 Suppl 6):20-7. Pubmed

3. Tubulin beta chain

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Tubulin beta chain P07437 Details

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

1. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2009 Nov 24. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13