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targets (3) enzymes (2)
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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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Podophyllinic acid lactone
Salts Not Available
Brand names
Name Company
Podophyllotoxin
Podophyllotoxin 7
Brand mixtures Not Available
Categories
  • Keratolytic Agents
  • Antineoplastic Agents, Phytogenic
  • Antimitotic agent
  • Tubulin Modulators
CAS number 477-47-4
Weight Average: 414.4053
Monoisotopic: 414.13146768
Chemical Formula C22H22O8
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Podophyllotoxins
Substructures
  • Podophyllotoxins
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Naphthalenes
  • Acetates
  • Acetals and Derivatives
  • Phenols and Derivatives
  • Lactones
  • Ethers
  • Benzene and Derivatives
  • Dioxoles
  • Catechols
  • Heterocyclic compounds
  • Aromatic compounds
  • Benzodioxoles
  • Anisoles
  • Furans
  • Alcohols and Polyols
  • Cyclohexenes and Derivatives
  • Phenyl Esters
Pharmacology
Indication For treatment of external genital warts (Condyloma acuminatum).
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
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
Pharmacoeconomics
Manufacturers
  • Watson pharmaceuticals inc
  • Collegium pharmaceutical inc
  • Paddock laboratories inc
Packagers
Dosage forms
Form Route Strength
Liquid Topical
Prices
Unit description Cost Unit
Podofilox 0.5% Solution 3.5ml Bottle 105.99 USD bottle
Condylox 0.5% gel 97.73 USD g
Wartec 0.5 % Solution 14.26 USD solution
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 228 °C PhysProp
water solubility 100 mg/L (at 25 °C) MERCK INDEX (1996)
logP 1.5 Not Available
Predicted Properties
Property Value Source
water solubility 1.14e-01 g/l ALOGPS
logP 2.37 ALOGPS
logP 1.62 ChemAxon
logS -3.6 ALOGPS
pKa (strongest acidic) 14.02 ChemAxon
pKa (strongest basic) -3.2 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 92.68 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 103.91 ChemAxon
polarizability 41.71 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C10871 Link_out
PubChem Compound 10607 Link_out
PubChem Substance 46505716 Link_out
ChemSpider 10162 Link_out
ChEBI 50305 Link_out
ChEMBL 50305 Link_out
Therapeutic Targets Database DNC001139 Link_out
PharmGKB PA450993 Link_out
HET POD Link_out
RxList http://www.rxlist.com/cgi/generic4/podophyllin.htm Link_out
Drugs.com http://www.drugs.com/cdi/podofilox-gel.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Podofilox Link_out
ATC Codes
  • D06BB04
AHFS Codes
  • 84:92.00
PDB Entries Not Available
FDA label Not Available
MSDS show (55.9 KB)
Interactions
Drug Interactions Searched, but no interactions found.
Food Interactions Not Available
Targets

1. DNA topoisomerase 2-alpha

Pharmacological action: yes
Actions: inhibitor

Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks

Organism class: human
UniProt ID: P11388 Link_out
Gene: TOP2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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-1 chain

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P68366 Link_out
Gene: TUBA4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P07437 Link_out
Gene: TUBB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 2C19

Actions: substrate

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 imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 February 08, 2013 16:19