Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Fostemsavir Action Pathway
Homo sapiens
Drug Action Pathway
Fostemsavir is the phosphonooxymethyl prodrug of temsavir, which is a HIV-1 attachment inhibitor that binds to the gp120 subunit within the HIV-1 gp160 envelope glycoprotein. Fostemavir is the first attachment inhibitor to receive FDA approval, granted in July 2020, for use in combination with other antretrovirals. The gp120 subunit within the gp160 envelpe glycoprotein of HIV-1 are responsible for facilitating attachment of the virus to the host cell CD4 receptors.
Fostemsavir is metabolized in the microvilli of the small intestine into temsavir by the enzyme Intestinal-type alkaline phosphatase. It is transported into the blood where temsavir inhibits the envelope glycoprotein of HIV-1 by binding directly to the gp120 subunit, which inhibits the viral interaction with host CD4 receptors, thereby preventing the initial attachment of the virus. It has also been shown to inhibit other gp120-dependent post-attachment steps required for viral entry. The inability for the virus to attach and release viral components into the host cell greatly reduces the replication of the virus.
References
Fostemsavir Pathway References
Meanwell NA, Krystal MR, Nowicka-Sans B, Langley DR, Conlon DA, Eastgate MD, Grasela DM, Timmins P, Wang T, Kadow JF: Inhibitors of HIV-1 Attachment: The Discovery and Development of Temsavir and its Prodrug Fostemsavir. J Med Chem. 2018 Jan 11;61(1):62-80. doi: 10.1021/acs.jmedchem.7b01337. Epub 2017 Dec 22.
Pubmed: 29271653
Moore K, Magee M, Sevinsky H, Chang M, Lubin S, Myers E, Ackerman P, Llamoso C: Methadone and buprenorphine pharmacokinetics and pharmacodynamics when coadministered with fostemsavir to opioid-dependent, human immunodeficiency virus seronegative participants. Br J Clin Pharmacol. 2019 Aug;85(8):1771-1780. doi: 10.1111/bcp.13964. Epub 2019 Jun 5.
Pubmed: 30980734
Wang T, Ueda Y, Zhang Z, Yin Z, Matiskella J, Pearce BC, Yang Z, Zheng M, Parker DD, Yamanaka GA, Gong YF, Ho HT, Colonno RJ, Langley DR, Lin PF, Meanwell NA, Kadow JF: Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir. J Med Chem. 2018 Jul 26;61(14):6308-6327. doi: 10.1021/acs.jmedchem.8b00759. Epub 2018 Jul 13.
Pubmed: 29920093
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings