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Pathway Description
Daunorubicin Action Pathway
Homo sapiens
Drug Action Pathway
Daunorubicin is an aminoglycoside used to induce remission of nonlymphocytic leukemia and acute lymphocytic leukemia (ALL). This drug is a very toxic anthracycline antineoplastic isolated from Streptomyces peucetius and is administered by injection into a vein. It inhibits cellular reproduction by interfering with DNA replication. Also, it may contribute to the induction of apoptosis by increasing the oxidative stress of the cell through the generation of reactive oxygen species and free radicals. Daunorubicin carries significant toxicities including cytopenias, hepatotoxicity, and extravasation reactions. Like other anthracyclines, daunorubicin exhibits cardiotoxicity that is in proportion to the cumulative dose of the drug. Daunorubicin acts by forming many complexes with DNA, by intercalation between base pairs, and it inhibits topoisomerase II (2-alpha and 2-beta) activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II normally catalyzes. By doing this, the cell will not be able to continue its replication and will die through apoptosis.
References
Daunorubicin 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
Balis FM, Holcenberg JS, Bleyer WA: Clinical pharmacokinetics of commonly used anticancer drugs. Clin Pharmacokinet. 1983 May-Jun;8(3):202-32. doi: 10.2165/00003088-198308030-00002.
Pubmed: 6189661
Cafaro A, Giannini MB, Silimbani P, Cangini D, Masini C, Ghelli Luserna Di Rora A, Simonetti G, Martinelli G, Cerchione C: CPX-351 daunorubicin-cytarabine liposome: a novel formulation to treat patients with newly diagnosed secondary acute myeloid leukemia. Minerva Med. 2020 Oct;111(5):455-466. doi: 10.23736/S0026-4806.20.07017-2. Epub 2020 Sep 21.
Pubmed: 32955826
Mayer LD, Tardi P, Louie AC: CPX-351: a nanoscale liposomal co-formulation of daunorubicin and cytarabine with unique biodistribution and tumor cell uptake properties. Int J Nanomedicine. 2019 May 23;14:3819-3830. doi: 10.2147/IJN.S139450. eCollection 2019.
Pubmed: 31213803
Saleem T, Kasi A: Daunorubicin.
Pubmed: 32644499
Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. doi: 10.1016/0300-9084(84)90018-x.
Pubmed: 6380596
Zunino F, Capranico G: DNA topoisomerase II as the primary target of anti-tumor anthracyclines. Anticancer Drug Des. 1990 Nov;5(4):307-17.
Pubmed: 1963303
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