rabacfosadine has been researched along with 9-(2-phosphonylmethoxyethyl)-2-6-diaminopurine* in 2 studies
1 review(s) available for rabacfosadine and 9-(2-phosphonylmethoxyethyl)-2-6-diaminopurine
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[Acyclic nucleoside phosphonates as potential antineoplastic agents].
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. Topics: Adenine; Alanine; Animals; Antineoplastic Agents; Cell Line, Tumor; Guanine; Humans; Lymphoma, Non-Hodgkin; Nucleosides; Organophosphonates; Organophosphorus Compounds; Purines | 2008 |
1 other study(ies) available for rabacfosadine and 9-(2-phosphonylmethoxyethyl)-2-6-diaminopurine
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Mutations in adenosine deaminase-like (ADAL) protein confer resistance to the antiproliferative agents N6-cyclopropyl-PMEDAP and GS-9219.
GS 9219 is a double prodrug of antiproliferative nucleotide analog 9-(2-Phosphonylmethoxyethyl)guanine (PMEG), with potent in vivo efficacy against various hematological malignancies. This study investigates the role of adenosine deaminase-like (ADAL) protein in the intracellular activation of GS-9219.. A cell line resistant to 9-(2-Phosphonylmethoxyethyl)-N(6)-cyclopropyl-2,6-diaminopurine (cPrPMEDAP), an intermediate metabolite of GS-9219, was generated and characterized.. The resistant cell line was cross-resistant to cPrPMEDAP and GS-9219, due to a defect in the deamination of cPrPMEDAP to PMEG. Mutations in the ADAL gene (H286R and S180N) were identified in the resistant cells that adversely-affected its enzymatic activity. Introduction of the wild-type ADAL gene re-sensitized resistant cells to both cPrPMEDAP and GS-9219.. The ADAL protein plays an essential role in the intracellular activation of GS-9219 by catalyzing the deamination of cPrPMEDAP metabolite to PMEG. Mutations affecting the activity of ADAL confer resistance to both GS-9219 and its metabolite cPrPMEDAP. Topics: Adenine; Alanine; Amino Acid Sequence; Antineoplastic Agents; Blotting, Western; Drug Resistance, Neoplasm; Female; Humans; Molecular Sequence Data; Mutation; Nucleoside Deaminases; Prodrugs; Protein Conformation; Purines; Sequence Homology, Amino Acid; Tumor Cells, Cultured; Uterine Cervical Neoplasms | 2013 |