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Pathway Description
Artesunate Action Pathway
Homo sapiens
Drug Action Pathway
Artesunate is artesunate is an artemesinin derivative indicated for the initial treatment of severe malaria. Artesunate is an artemisinin derivative that is metabolized to DHA, which generates free radicals to inhibit normal function of Plasmodium parasites.
Artesunate is metabolized in the liver to the active DHA. DHA enters the Plasmodium parasite. Once in the parasite iDHA reacts with heme, which generats free radicals which inhibit protein and nucleic acid synthesis of the Plasmodium parasites. Reactions with these free radicals can also lead to alkylation of parasitic proteins such as a calcium adenosine triphosphatase and EXP1, a glutathione S-transferase.
References
Artesunate Pathway References
Fry ET, Mack DL, Sobel BE: The nature of synergy between tissue-type and single chain urokinase-type plasminogen activators. Thromb Haemost. 1989 Nov 24;62(3):909-16.
Pubmed: 2512679
Ilett KF, Ethell BT, Maggs JL, Davis TM, Batty KT, Burchell B, Binh TQ, Thu le TA, Hung NC, Pirmohamed M, Park BK, Edwards G: Glucuronidation of dihydroartemisinin in vivo and by human liver microsomes and expressed UDP-glucuronosyltransferases. Drug Metab Dispos. 2002 Sep;30(9):1005-12. doi: 10.1124/dmd.30.9.1005.
Pubmed: 12167566
Li Q, Xie LH, Haeberle A, Zhang J, Weina P: The evaluation of radiolabeled artesunate on tissue distribution in rats and protein binding in humans. Am J Trop Med Hyg. 2006 Nov;75(5):817-26.
Pubmed: 17123971
Veerappan A, Eichhorn T, Zeino M, Efferth T, Schneider D: Differential interactions of the broad spectrum drugs artemisinin, dihydroartemisinin and artesunate with serum albumin. Phytomedicine. 2013 Aug 15;20(11):969-74. doi: 10.1016/j.phymed.2013.04.003. Epub 2013 May 16.
Pubmed: 23684544
Artesunate Product Information https://extranet.who.int/pqweb/
FDA Approved Drug Products: Artesunate Intravenous Injection https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213036s000lbl.pdf
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
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