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Pathway Description
Podofilox Action Pathway
Homo sapiens
Drug Action Pathway
Podofilox, also called podophyllotoxin or Condylox, is a topical agent used for the treatment of external genital warts (Condyloma acuminatum) and perianal warts.This drugs comes from the roots of podophyllum plants. It is very irritating to skin and mucous membranes, has keratolytic actions and may have antineoplastic properties. The exact mechanism of action is not well understood, but it does appear that Podofilox and its derivatives may bind and inhibit topoisomerase II during late S and early G2 stages of the cell mitosis. The drug possibly binds and stabilizes the temporary break caused by topoisomerase II. This disrupts the reparation of the break through which double-stranded DNA passes and therefore, stops DNA unwinding and replication. This drug is also studied as a possible tubulin alpha-4A and tubulin beta chains inhibitor. It is available as a topical solution.
References
Podofilox Pathway References
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. doi: 10.1248/cpb.48.486.
Pubmed: 10783066
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
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. doi: 10.1248/cpb.40.2720.
Pubmed: 1334447
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. doi: 10.1016/j.bmc.2005.06.032. Epub 2005 Aug 2.
Pubmed: 16061385
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. doi: 10.1093/nar/30.1.412.
Pubmed: 11752352
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
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
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