Loading Pathway...

Pathway Description

Cidofovir Action Pathway

Homo sapiens

Category:

Metabolite Pathway

Sub-Category:

Drug Action

Created: 2023-02-23

Last Updated: 2023-10-25

Cidofovir is an injectable antiviral agent used to treat Cytomegalovirus (CMV) retinitis in patients with AIDS. It was manufactured by Gilead and initially approved by the FDA in 1996, but has since been discontinued. Cidofovir acts through the selective inhibition of viral DNA polymerase. After incorporation into the host cell, cidofovir is phosphorylated by pyruvate kinases to the active metabolite cidofovir diphosphate. Cidofovir diphosphate inhibits herpesvirus polymerases at concentrations that are 8- to 600-fold lower than those needed to inhibit human cellular DNA polymerase alpha, beta, and gamma(1,2,3). Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis. Less Viral DNA is transported into the nucleus, therefore, less viral DNA is integrated into the host DNA. Less viral proteins produced, fewer viruses can form.

References

Cidofovir Pathway References

National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 60613, Cidofovir. Retrieved February 24, 2023 from https://pubchem.ncbi.nlm.nih.gov/compound/Cidofovir.

https://ncithesaurus.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C77925

https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020638

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. doi: 10.1038/nrd2199.

Pubmed: 17139284

Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. doi: 10.1038/nrd2132.

Pubmed: 17016423

Magee WC, Hostetler KY, Evans DH: Mechanism of inhibition of vaccinia virus DNA polymerase by cidofovir diphosphate. Antimicrob Agents Chemother. 2005 Aug;49(8):3153-62. doi: 10.1128/AAC.49.8.3153-3162.2005.

Pubmed: 16048917

Sergerie Y, Boivin G: Hydroxyurea enhances the activity of acyclovir and cidofovir against herpes simplex virus type 1 resistant strains harboring mutations in the thymidine kinase and/or the DNA polymerase genes. Antiviral Res. 2008 Jan;77(1):77-80. doi: 10.1016/j.antiviral.2007.08.009. Epub 2007 Sep 17.

Pubmed: 17913252

Gilbert C, Boivin G: New reporter cell line to evaluate the sequential emergence of multiple human cytomegalovirus mutations during in vitro drug exposure. Antimicrob Agents Chemother. 2005 Dec;49(12):4860-6. doi: 10.1128/AAC.49.12.4860-4866.2005.

Pubmed: 16304146

Andrei G, De Clercq E, Snoeck R: Drug targets in cytomegalovirus infection. Infect Disord Drug Targets. 2009 Apr;9(2):201-22. doi: 10.2174/187152609787847758.

Pubmed: 19275707

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

Kanno H, Fujii H, Hirono A, Miwa S: cDNA cloning of human R-type pyruvate kinase and identification of a single amino acid substitution (Thr384----Met) affecting enzymatic stability in a pyruvate kinase variant (PK Tokyo) associated with hereditary hemolytic anemia. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8218-21. doi: 10.1073/pnas.88.18.8218.

Pubmed: 1896471

Tani K, Fujii H, Nagata S, Miwa S: Human liver type pyruvate kinase: complete amino acid sequence and the expression in mammalian cells. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1792-5. doi: 10.1073/pnas.85.6.1792.

Pubmed: 3126495

Kanno H, Fujii H, Miwa S: Structural analysis of human pyruvate kinase L-gene and identification of the promoter activity in erythroid cells. Biochem Biophys Res Commun. 1992 Oct 30;188(2):516-23. doi: 10.1016/0006-291x(92)91086-6.

Pubmed: 1445295

Highlighted elements will appear in red.

Highlight Compounds

	Cidofovir
	Cidofovir diphosphate
	dGTP
	Magnesium
	Potassium
	Pyrophosphate

Highlight Proteins

	DNA polymerase catalytic subunit
	Pyruvate kinase isozymes R/L
	Unknown

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