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Pathway Description
Penciclovir Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-02-23
Last Updated: 2023-10-25
Penciclovir is a topical nucleoside polymerase inhibitor used in the treatment of various herpes simplex virus (HSV) infections. Penciclovir has in vitro activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). In cells infected with HSV-1 or HSV-2, viral thymidine kinase phosphorylates penciclovir to a monophosphate form. The monophosphate form of the drug is then converted to penciclovir triphosphate by cellular kinases.
Penciclovir triphosphate inhibits the activity of DNA polymerase by competing with its substrate dGTP. 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
Penciclovir Pathway References
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020629s019lbl.pdf
Rosengard AM, Krutzsch HC, Shearn A, Biggs JR, Barker E, Margulies IM, King CR, Liotta LA, Steeg PS: Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development. Nature. 1989 Nov 9;342(6246):177-80. doi: 10.1038/342177a0.
Pubmed: 2509941
Gilles AM, Presecan E, Vonica A, Lascu I: Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J Biol Chem. 1991 May 15;266(14):8784-9.
Pubmed: 1851158
Wang L, Patel U, Ghosh L, Chen HC, Banerjee S: Mutation in the nm23 gene is associated with metastasis in colorectal cancer. Cancer Res. 1993 Feb 15;53(4):717-20.
Pubmed: 7916650
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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