1. [Acyclic nucleoside phosphonates as potential antineoplastic agents].
- Author
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Votruba I, Otová B, and Holý A
- Subjects
- Adenine analogs & derivatives, Adenine pharmacology, Adenine therapeutic use, Alanine analogs & derivatives, Alanine pharmacology, Alanine therapeutic use, Animals, Cell Line, Tumor drug effects, Guanine analogs & derivatives, Guanine pharmacology, Guanine therapeutic use, Humans, Lymphoma, Non-Hodgkin drug therapy, Organophosphorus Compounds pharmacology, Organophosphorus Compounds therapeutic use, Purines pharmacology, Purines therapeutic use, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Nucleosides pharmacology, Nucleosides therapeutic use, Organophosphonates pharmacology, Organophosphonates therapeutic use
- Abstract
Recently, Gilead Sciences (Foster City, CA, USA) presented a potential cytostatic drug GS-9219. It is a novel lipophilic prodrug of cyprPMEDAP, in vivo releasing the active compound PMEG in a two-step process. GS-9219 has shown a substantial therapeutic potential in treatment of spontaneous non-Hodgkin's lymphoma in dogs and its utilization in the human medicine is prospective. Hence, cyprPMEDAP represents a key intermediate in the intracellular activation of GS-9219. Both acyclic nucleoside phosphonates PMEG and cyprPMEDAP, serving as the basis for development of GS-9219, were discovered and their mechanism of action was investigated in detail at the Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic. The biological studies using the rat lymphoma were carried out at the First Faculty of Medicine, Charles University.
- Published
- 2008