Most cited article - PubMed ID 2342627
The cytostatic effects and mechanism of action of antiviral acyclic adenine nucleotide analogs in L1210 mouse leukemia cells
Tenofovir diphosphate (PMPApp) is a weak inhibitor of DNA polymerases (pol) alpha, delta, and epsilon*, with values for the Ki for PMPApp ((PMPApp)Ki) relative to the Km for dATP ((dATP)Km) of 10.2, 10.2, and 15.2, respectively. Its incorporation into DNA was about 1,000-fold less efficient than that of dATP, with (PMPApp)Km values 350-, 2,155-, and 187-fold higher than (dATP)Km values for pol alpha, delta, and epsilon*, respectively.
- MeSH
- Adenine analogs & derivatives metabolism pharmacology MeSH
- DNA-Directed DNA Polymerase metabolism MeSH
- DNA Polymerase I antagonists & inhibitors metabolism MeSH
- DNA Polymerase II antagonists & inhibitors metabolism MeSH
- DNA Polymerase III antagonists & inhibitors metabolism MeSH
- Reverse Transcriptase Inhibitors metabolism pharmacology MeSH
- Nucleic Acid Synthesis Inhibitors * MeSH
- Rats MeSH
- Anti-HIV Agents metabolism pharmacology MeSH
- Organophosphonates * MeSH
- Organophosphorus Compounds metabolism pharmacology MeSH
- Tenofovir MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adenine MeSH
- DNA-Directed DNA Polymerase MeSH
- DNA Polymerase I MeSH
- DNA Polymerase II MeSH
- DNA Polymerase III MeSH
- Reverse Transcriptase Inhibitors MeSH
- Nucleic Acid Synthesis Inhibitors * MeSH
- Anti-HIV Agents MeSH
- Organophosphonates * MeSH
- Organophosphorus Compounds MeSH
- Tenofovir MeSH
The nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG) has been identified as a powerful antiproliferative substance when acting on hybridoma cells. In the range of 10 nM to 100 nM concentrations this agent reduces cell growth rate, while its apoptosis-inducing activity is marginal. Marked induction of apoptosis can be observed at micromolar and higher order concentrations. In PMEG-supplemented media the cell cycle progression is perturbed, the flow-cytometric DNA profile shows a higher proportion of cells in the S and G2/M phases of the cell cycle. Concomitantly with the reduction of the growth rate, the specific monoclonal antibody production rate may rise by 20-27%. Addition of PMEG at the end of the exponential phase of a batch culture results in an enhancement of the final monoclonal antibody concentration.
- Publication type
- Journal Article MeSH
