What enzyme activates ganciclovir?
Ganciclovir is metabolized to the triphosphate form by primarily three cellular enzymes: (1) a deoxy- guanosine kinase induced by CMV-infected cells; (2) guanylate kinase; and (3) phospho- glycerate kinase. Other nucleotide-metabolizing enzymes may be involved as well.
What does thymidine kinase do?
Thymidine kinase (TK) activity is measured by radioenzymatic assay. TK is an enzyme that catalyses the phosphorylation of deoxythymidine to deoxythymidine monophosphate. Its activity is highest in G1-S translation checkpoint and then declines rapidly in the G2 phase of the cell cycle.
What is HSV TK?
Definition. A form of suicide gene therapy in which the cDNA for a viral enzyme, the herpes simplex virus thymidine kinase (HSV-TK), is transferred to tumor cells followed by treatment with the antiviral drug ganciclovir (GCV). Expression of HSV-TK enables cells to phosphorylate GCV to a monophosphate derivative.
How is ganciclovir activated?
Mechanism of action. Ganciclovir is a synthetic analogue of 2′-deoxy-guanosine. It is first phosphorylated to ganciclovir monophosphate by a viral kinase encoded by the cytomegalovirus (CMV) gene UL97 during infection.
Which is active form of ganciclovir?
Ganciclovir is metabolized to the triphosphate form by primarily three cellular enzymes: (1) a deoxyguanosine kinase induced by CMV-infected cells; (2) guanylate kinase; and (3) phosphoglycerate kinase.
Does CMV have thymidine kinase?
The major difference is that CMV does not contain a thymidine kinase. Protein UL97 phosphorylates ganciclovir to ganciclovir monophosphate. One of the mechanisms of ganciclovir resistance is a change in UL97.
How does HSV TK work?
HSV-1 is mainly transmitted by oral-to-oral contact to cause oral herpes infection, via contact with the HSV-1 virus in sores, saliva, and surfaces in or around the mouth. However, HSV-1 can also be transmitted to the genital area through oral-genital contact to cause genital herpes.
Why is ganciclovir toxic to cells that are expressing the viral thymidine kinase enzyme?
This high toxicity may be attributable to the avid incorporation and lengthy retention of GCV into DNA. GCV triphosphate and its incorporation into the nascent DNA strand do not produce strong inhibition of DNA synthesis, so cells incorporate high levels of this drug, complete DNA replication and go on to divide.
Who manufactures ganciclovir?
Ranbaxy Laboratories Ltd.
Ganciclovir (500 mg) Manufacturer: Ranbaxy Laboratories Ltd.
What is ganciclovir cytomegalovirus?
Ganciclovir (9-(1,3-dihydroxy-2-propoxymethyl) guanine, DHPG) is an acyclovir analog with excellent antiviral activity against human cytomegalovirus (CMV). Clinically, CMV infection occurs in from 60 to 90% of all renal transplant recipients and it is responsible for significant patient morbidity and graft loss.
How is ganciclovir metabolized?
Ganciclovir is metabolized to the triphosphate form by primarily three cellular enzymes: (1) a deoxyguanosine kinase induced by CMV-infected cells; (2) guanylate kinase; and (3) phosphoglycerate kinase. Other nucleotide-metabolizing enzymes may be involved as well.
