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Pathway Description
Cabotegravir Action Pathway
Homo sapiens
Drug Action Pathway
Cabotegravir is an HIV-1 integrase inhibitor used for treatment and pre-exposure prophylaxis of HIV-1 infection. It is prescribed with the non-nucleoside reverse transcriptase inhibitor, rilpivirine.
Cabotegravir is transported into the infected cell then transported into the nucleus via importin nuclear transporter. The viral RNA is injected into the cell then transcribed into viral DNA via reverse transcriptase. It is then transported into the nucleus where it is integrated into the host DNA. Cabotegravir inhibits HIV integrase which prevents the viral DNA from being integrated into the host DNA. This prevents viral replication and further progression of the virus. It is used in combination with reverse transcriptase inhibitors which further prevents viral replication and progression of the virus.
References
Cabotegravir Pathway References
Patel M, Eberl HC, Wolf A, Pierre E, Polli JW, Zamek-Gliszczynski MJ: Mechanistic Basis of Cabotegravir-Glucuronide Disposition in Humans. J Pharmacol Exp Ther. 2019 Aug;370(2):269-277. doi: 10.1124/jpet.119.258384. Epub 2019 Jun 7.
Pubmed: 31175220
Spreen W, Min S, Ford SL, Chen S, Lou Y, Bomar M, St Clair M, Piscitelli S, Fujiwara T: Pharmacokinetics, safety, and monotherapy antiviral activity of GSK1265744, an HIV integrase strand transfer inhibitor. HIV Clin Trials. 2013 Sep-Oct;14(5):192-203. doi: 10.1310/hct1405-192.
Pubmed: 24144896
Johns BA, Kawasuji T, Weatherhead JG, Taishi T, Temelkoff DP, Yoshida H, Akiyama T, Taoda Y, Murai H, Kiyama R, Fuji M, Tanimoto N, Jeffrey J, Foster SA, Yoshinaga T, Seki T, Kobayashi M, Sato A, Johnson MN, Garvey EP, Fujiwara T: Carbamoyl pyridone HIV-1 integrase inhibitors 3. A diastereomeric approach to chiral nonracemic tricyclic ring systems and the discovery of dolutegravir (S/GSK1349572) and (S/GSK1265744). J Med Chem. 2013 Jul 25;56(14):5901-16. doi: 10.1021/jm400645w. Epub 2013 Jul 11.
Pubmed: 23845180
Shaik JSB, Ford SL, Lou Y, Zhang Z, Bakshi KK, Tenorio AR, Trezza C, Spreen WR, Patel P: A Phase 1 Study to Evaluate the Pharmacokinetics and Safety of Cabotegravir in Patients With Hepatic Impairment and Healthy Matched Controls. Clin Pharmacol Drug Dev. 2019 Jul;8(5):664-673. doi: 10.1002/cpdd.655. Epub 2019 Feb 27.
Pubmed: 30811880
https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Vocabria/pdf/VOCABRIA-PI-PIL.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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