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Pathway Description
Podofilox Action Pathway (New)
Homo sapiens
Drug Action Pathway
Podofilox, also known as Condylox or podophyllotoxin, is an agent used for the treatment of external genital warts (Condyloma acuminatum) and perianal warts. This drug comes from the roots of podophyllum plants. 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. The exact mechanism of action is not clear. It possibly binds and inhibits topoisomerase II during the late S and early G2 stages. This disrupts the reparation of the breaks through which the double-stranded DNA passes. This stops the natural DNA unwinding and, in consequence, the replication of the DNA. The binding and inhibition of the tubulin chain of this drug are also studied. Podofilox is administered as a topical gel/solution only.
References
Podofilox Pathway (New) References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
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
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
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
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
Clark PI: Clinical pharmacology and schedule dependency of the podophyllotoxin derivatives. Semin Oncol. 1992 Apr;19(2 Suppl 6):20-7.
Pubmed: 1411635
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. doi: 10.1021/np50086a011.
Pubmed: 1331331
Ruckdeschel JC: Etoposide in the management of non-small cell lung cancer. Cancer. 1991 Jan 1;67(1 Suppl):250-3. doi: 10.1002/1097-0142(19910101)67:1+<250::aid-cncr2820671307>3.0.co;2-9.
Pubmed: 1845848
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