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Pathway Description
Idarubicin Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-05-25
Last Updated: 2023-10-25
Idarubicin is an antineoplastic agent used to treat acute myeloid leukemia (AML) in adults. This drug, from the anthracycline class, is orally administered and has shown activity against breast cancer, lymphomas, and leukemias. Idarubicin has antimitotic and cytotoxic activity. Firstly, idarubicin forms complexes with DNA by intercalation. Secondly, it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex when it binds to the DNA topoisomerase 2-alpha subunit, this prevents the religation portion of the ligation-religation reaction that is naturally catalyzed by this topoisomerase. Idarubicin may also inhibit polymerase activity, affect the regulation of gene expression, and produce free radical damage to DNA. Idarubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. Idarubicin is cell cycle-nonspecific.
References
Idarubicin Pathway 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
Zahraei Z, Rabbani-Chadegani A: A comparison of the effect of anticancer drugs, idarubicin and adriamycin, on soluble chromatin. Eur J Pharmacol. 2007 Dec 1;575(1-3):28-33. doi: 10.1016/j.ejphar.2007.07.045. Epub 2007 Jul 31.
Pubmed: 17716648
Hollingshead LM, Faulds D: Idarubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. Drugs. 1991 Oct;42(4):690-719. doi: 10.2165/00003495-199142040-00010.
Pubmed: 1723369
Bigioni M, Zunino F, Capranico G: Base mutation analysis of topoisomerase II-idarubicin-DNA ternary complex formation. Evidence for enzyme subunit cooperativity in DNA cleavage. Nucleic Acids Res. 1994 Jun 25;22(12):2274-81. doi: 10.1093/nar/22.12.2274.
Pubmed: 8036155
Fukushima T, Ueda T, Uchida M, Nakamura T: Action mechanism of idarubicin (4-demethoxydaunorubicin) as compared with daunorubicin in leukemic cells. Int J Hematol. 1993 Apr;57(2):121-30.
Pubmed: 8494991
Gonzalez-Cid M, Fundia AF, Cuello MT, Larripa I: Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes. Toxicology. 2002 Feb 28;171(2-3):215-22. doi: 10.1016/s0300-483x(01)00596-0.
Pubmed: 11836027
Tsai-Pflugfelder M, Liu LF, Liu AA, Tewey KM, Whang-Peng J, Knutsen T, Huebner K, Croce CM, Wang JC: Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7177-81. doi: 10.1073/pnas.85.19.7177.
Pubmed: 2845399
Wasserman RA, Austin CA, Fisher LM, Wang JC: Use of yeast in the study of anticancer drugs targeting DNA topoisomerases: expression of a functional recombinant human DNA topoisomerase II alpha in yeast. Cancer Res. 1993 Aug 1;53(15):3591-6.
Pubmed: 8393377
Lang AJ, Mirski SE, Cummings HJ, Yu Q, Gerlach JH, Cole SP: Structural organization of the human TOP2A and TOP2B genes. Gene. 1998 Oct 23;221(2):255-66. doi: 10.1016/s0378-1119(98)00468-5.
Pubmed: 9795238
Uchiumi T, Hinoshita E, Haga S, Nakamura T, Tanaka T, Toh S, Furukawa M, Kawabe T, Wada M, Kagotani K, Okumura K, Kohno K, Akiyama S, Kuwano M: Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport. Biochem Biophys Res Commun. 1998 Nov 9;252(1):103-10. doi: 10.1006/bbrc.1998.9546.
Pubmed: 9813153
Kiuchi Y, Suzuki H, Hirohashi T, Tyson CA, Sugiyama Y: cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3). FEBS Lett. 1998 Aug 14;433(1-2):149-52. doi: 10.1016/s0014-5793(98)00899-0.
Pubmed: 9738950
Belinsky MG, Bain LJ, Balsara BB, Testa JR, Kruh GD: Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. J Natl Cancer Inst. 1998 Nov 18;90(22):1735-41. doi: 10.1093/jnci/90.22.1735.
Pubmed: 9827529
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