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Pathway Description
Baloxavir marboxil Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-05-05
Last Updated: 2023-10-25
Baloxavir marboxil is a polymerase acidic endonuclease inhibitor used to treat uncomplicated influenza A, B, and Avian. It is specifically a first-in-class cap-dependent endonuclease inhibitor. It is a prodrug of baloxavir with an improved absorption profile than its active metabolite due to the addition of a phenolic hydroxyl group to its structure.
Influenza virus RNA polymerase is made up of three subunits: polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), and polymerase acidic protein (PA). The PB2 subunit binds to the cap of host cellular pre-messenger RNA, which allows the polymerase acidic protein to cleave the capped pre-messenger RNA.This is the initial step of mRNA synthesis so viral mRNA transcription can occur.
After administration, the prodrug baloxavir marboxil is almost completely hydrolyzed by esterases in the gastrointestinal lumen, intestinal epithelium, liver and blood to its active metabolite, baloxavir. Balaxovir selectively inhibits the polymerase acidic protein, which blocks the initiation of mRNA synthesis which prevents influenza virus proliferation.
References
Baloxavir marboxil Pathway References
Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, Ishida T, Sekino H, Yamada K, Portsmouth S, Kawaguchi K, Shishido T, Arai M, Tsuchiya K, Uehara T, Watanabe A: Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med. 2018 Sep 6;379(10):913-923. doi: 10.1056/NEJMoa1716197.
Pubmed: 30184455
Heo YA: Baloxavir: First Global Approval. Drugs. 2018 Apr;78(6):693-697. doi: 10.1007/s40265-018-0899-1.
Pubmed: 29623652
Shirley M: Baloxavir Marboxil: A Review in Acute Uncomplicated Influenza. Drugs. 2020 Jul;80(11):1109-1118. doi: 10.1007/s40265-020-01350-8.
Pubmed: 32601915
Abraham GM, Morton JB, Saravolatz LD: Baloxavir: A Novel Antiviral Agent in the Treatment of Influenza. Clin Infect Dis. 2020 Oct 23;71(7):1790-1794. doi: 10.1093/cid/ciaa107.
Pubmed: 32020174
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
Janke D, Mehralivand S, Strand D, Godtel-Armbrust U, Habermeier A, Gradhand U, Fischer C, Toliat MR, Fritz P, Zanger UM, Schwab M, Fromm MF, Nurnberg P, Wojnowski L, Closs EI, Lang T: 6-mercaptopurine and 9-(2-phosphonyl-methoxyethyl) adenine (PMEA) transport altered by two missense mutations in the drug transporter gene ABCC4. Hum Mutat. 2008 May;29(5):659-69. doi: 10.1002/humu.20694.
Pubmed: 18300232
Lee K, Belinsky MG, Bell DW, Testa JR, Kruh GD: Isolation of MOAT-B, a widely expressed multidrug resistance-associated protein/canalicular multispecific organic anion transporter-related transporter. Cancer Res. 1998 Jul 1;58(13):2741-7.
Pubmed: 9661885
Adachi M, Sampath J, Lan LB, Sun D, Hargrove P, Flatley R, Tatum A, Edwards MZ, Wezeman M, Matherly L, Drake R, Schuetz J: Expression of MRP4 confers resistance to ganciclovir and compromises bystander cell killing. J Biol Chem. 2002 Oct 11;277(41):38998-9004. doi: 10.1074/jbc.M203262200. Epub 2002 Jun 24.
Pubmed: 12105214
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