Studies on the Mechanism of Action of Benzamide Riboside: A Novel Inhibitor of IMP Dehydrogenase

2002 ◽  
Vol 9 (7) ◽  
pp. 743-748 ◽  
Author(s):  
Kamran Gharehbaghi ◽  
Werner Grunberger ◽  
Hiremagalur Jayaram
Keyword(s):  
Mechanism Of Action ◽  
Imp Dehydrogenase ◽  
Benzamide Riboside

Cytotoxicity of a new IMP dehydrogenase inhibitor, benzamide riboside, to human myelogenous leukemia K562 cells

1992 ◽  
Vol 186 (3) ◽  
pp. 1600-1606 ◽  
Author(s):  
Hiremagalur N. Jayaram ◽  
Kamran Gharehbaghi ◽  
Nagesh H. Jayaram ◽  
Jason Rieser ◽  
Karsten Krohn ◽  
...  
Keyword(s):  
K562 Cells ◽  
Myelogenous Leukemia ◽  
Imp Dehydrogenase ◽  
Benzamide Riboside

Role of Human Nucleoside Transporters in the Cellular Uptake of Two Inhibitors of IMP Dehydrogenase, Tiazofurin and Benzamide Riboside

2004 ◽  
Vol 67 (1) ◽  
pp. 273-279 ◽  
Author(s):  
Vijaya L. Damaraju ◽  
Frank Visser ◽  
Jing Zhang ◽  
Delores Mowles ◽  
Amy M. L. Ng ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Nucleoside Transporters ◽  
Imp Dehydrogenase ◽  
Benzamide Riboside

Metabolism of the Novel IMP Dehydrogenase Inhibitor Benzamide Riboside

2002 ◽  
Vol 9 (7) ◽  
pp. 781-786 ◽  
Author(s):  
Walter Jager ◽  
Alexandra Salamon ◽  
Thomas Szekeres
Keyword(s):  
The Novel ◽  
Imp Dehydrogenase ◽  
Benzamide Riboside

Metabolism of the Novel IMP Dehydrogenase Inhibitor Benzamide Riboside

2004 ◽  
Vol 1 (2) ◽  
pp. 225-229
Author(s):  
Walter Jager ◽  
Alexandra Salamon ◽  
Thomas Szekeres
Keyword(s):  
The Novel ◽  
Imp Dehydrogenase ◽  
Benzamide Riboside

scholarly journals The Predominant Mechanism by Which Ribavirin Exerts Its Antiviral Activity In Vitro against Flaviviruses and Paramyxoviruses Is Mediated by Inhibition of IMP Dehydrogenase

2005 ◽  
Vol 79 (3) ◽  
pp. 1943-1947 ◽  
Author(s):  
Pieter Leyssen ◽  
Jan Balzarini ◽  
Erik De Clercq ◽  
Johan Neyts
Keyword(s):  
Antiviral Activity ◽  
Dehydrogenase Activity ◽  
Mechanism Of Action ◽  
Mycophenolic Acid ◽  
Linear Correlation ◽  
Compelling Evidence ◽  
Imp Dehydrogenase ◽  
Antiviral Activities

ABSTRACT It is not yet clear to what extent depletion of intracellular GTP pools contributes to the antiviral activity of ribavirin. Therefore, the antiviral activities of (i) ribavirin, (ii) its 5-ethynyl analogue, 5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamide (EICAR), and (iii) mycophenolic acid (MPA) (a compound that inhibits only cellular IMP dehydrogenase activity) were studied on the replication of flaviviruses and paramyxoviruses. In addition, the effects of these three compounds on intracellular GTP pools were assessed. A linear correlation was observed over a broad concentration range between the antiviral activities of ribavirin, EICAR, and MPA and the effects of these compounds on GTP pool depletion. When the 50% effective concentrations (EC50s) for the antiviral activities of ribavirin, EICAR, and MPA were plotted against the respective EC50 values for GTP pool depletion, a linear correlation was calculated. These data provide compelling evidence that the predominant mechanism of action of ribavirin in vitro against flavi- and paramyxoviruses is based on inhibition of cellular IMP dehydrogenase activity.

Comparison of biochemical parameters of benzamide riboside, a new inhibitor of IMP dehydrogenase, with tiazofurin and selenazofurin

1994 ◽  
Vol 48 (7) ◽  
pp. 1413-1419 ◽  
Author(s):  
Kamran Gharehbaghi ◽  
Ajay Sreenath ◽  
Zhang Hao ◽  
Kenneth D. Paull ◽  
Thomas Szekeres ◽  
...  
Keyword(s):  
Biochemical Parameters ◽  
Imp Dehydrogenase ◽  
Benzamide Riboside

Cytotoxicity and characterization of an active metabolite of benzamide riboside, a novel inhibitor of IMP dehydrogenase

1994 ◽  
Vol 56 (6) ◽  
pp. 892-899 ◽  
Author(s):  
Kamran Gharehbaghi ◽  
Kenneth D. Paull ◽  
James A. Kelley ◽  
Joseph J. Barchi ◽  
Victor E. Marquez ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Imp Dehydrogenase ◽  
Benzamide Riboside

scholarly journals Activity of Ribavirin against Hantaan Virus Correlates with Production of Ribavirin-5′-Triphosphate, Not with Inhibition of IMP Dehydrogenase

2006 ◽  
Vol 51 (1) ◽  
pp. 84-88 ◽  
Author(s):  
Yanjie Sun ◽  
Dong-Hoon Chung ◽  
Yong-Kyu Chu ◽  
Colleen B. Jonsson ◽  
William B. Parker
Keyword(s):  
Mechanism Of Action ◽  
Broad Spectrum ◽  
Antiviral Agent ◽  
Viral Rna ◽  
Hantaan Virus ◽  
Small Decrease ◽  
Secondary Importance ◽  
Imp Dehydrogenase ◽  
Dose Dependent ◽  
Primary Action

ABSTRACT Ribavirin (RBV) is a broad-spectrum antiviral agent that inhibits the production of infectious Hantaan virus (HTNV). Although the mechanism of action of RBV against HTNV is not understood, RBV is metabolized in human cells to both RBV-5′-monophosphate, which inhibits IMP dehydrogenase, resulting in a decrease in intracellular GTP levels, and RBV-5′-triphosphate (RBV-TP), which could selectively interact with the viral RNA polymerase. To elucidate which activity of RBV was most important to its anti-HTNV activity, the mechanism of action of RBV was studied in Vero E6 cells. Incubation with 10 to 40 μg/ml RBV resulted in a small decrease in GTP levels that was not dose dependent. Increasing the RBV concentration from 10 to 40 μg/ml resulted in a decrease in viral RNA (vRNA) levels and an increase in RBV-TP formation. Mycophenolic acid (MPA), an inhibitor of IMP dehydrogenase, also resulted in a decrease in vRNA levels; however, treatment with MPA resulted in a much greater decrease in GTP levels than that seen with RBV. Treatment with both MPA and RBV resulted in increased reduction of vRNA levels but did not result in enhanced depression of GTP levels. Although guanosine prevented the depression in GTP levels caused by RBV, guanosine only partially prevented the effect of RBV on vRNA levels. These results suggest that the inhibition of IMP dehydrogenase by RBV is of secondary importance to the inhibition of vRNA replication by RBV and that the interaction of RBV-TP with the viral polymerase is the primary action of RBV.

Studies on the mechanism of action of tiazofurin metabolism to an analog of NAD with potent IMP dehydrogenase-inhibitory activity

1983 ◽  
Vol 21 ◽  
pp. 271-303 ◽  
Author(s):  
David A. Cooney ◽  
Hiremagalur N. Jayaram ◽  
Robert I. Glazer ◽  
James A. Kelley ◽  
Victor E. Marquez ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Inhibitory Activity ◽  
Imp Dehydrogenase
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