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

The Antiherpesvirus Activity of H2G [(R)-9-[4-Hydroxy-2-(Hydroxymethyl)Butyl]Guanine] Is Markedly Enhanced by the Novel Immunosuppressive Agent Mycophenolate Mofetil

1998 ◽  
Vol 42 (12) ◽  
pp. 3285-3289 ◽  
Author(s):  
Johan Neyts ◽  
Graciela Andrei ◽  
Erik De Clercq
Keyword(s):  
Mycophenolate Mofetil ◽  
Parent Compound ◽  
Immunosuppressive Agent ◽  
The Novel ◽  
Kidney Transplant Recipients ◽  
Imp Dehydrogenase ◽  
Varicella Zoster ◽  
Antiviral Efficacy ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Mycophenolate mofetil (MMF) has been approved as an immunosuppressive agent in kidney transplant recipients and may thus be used concomitantly with antiherpetic agents, which are used for the treatment of intercurrent herpesvirus infections. We have recently demonstrated that MMF and its parent compound mycophenolic acid (MPA), which is a potent inhibitor of IMP dehydrogenase, potentiate the antiherpesvirus activity of acyclovir, ganciclovir, and penciclovir. We have now evaluated the antiviral efficacy of the combination of MPA and the novel antiherpesvirus agent H2G [(R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine]. When combined with H2G, MPA (at concentrations ranging from 0.25 to 10 μg/ml, which are readily attainable in human plasma) markedly potentiated the antiviral efficacy of H2G against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), as reflected by a 10- to 150-fold decrease in the 50% effective concentration. Moreover, the activity of H2G against a thymidine kinase-deficient strain of HSV-1 (TK− HSV-1) was increased more than 2,500-fold when combined with MPA. MPA by itself had little or no effect on the replication of these viruses. Similar observations were made for varicella-zoster virus. Also, ribavirin (another inhibitor of IMP dehydrogenase) caused a marked enhancement of the activity of H2G against HSV-1 (10-fold), HSV-2 (10-fold), and TK− HSV-1 (>185-fold). Exogenously added guanosine reversed the potentiating effects of MPA on the antiviral activity of H2G, indicating that this potentiating effect resulted from a depletion of the endogenous dGTP pools, thus favoring the inhibitory action of the H2G triphosphate on the viral DNA polymerase.

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

scholarly journals Assay method for monitoring the inhibitory effects of antimetabolites on the activity of inosinate dehydrogenase in intact human CEM lymphocytes

1992 ◽  
Vol 287 (3) ◽  
pp. 785-790 ◽  
Author(s):  
J Balzarini ◽  
E De Clercq
Keyword(s):  
Mycophenolic Acid ◽  
Marked Effect ◽  
De Novo ◽  
Potent Inhibitor ◽  
Assay Method ◽  
The Novel ◽  
Inhibitory Effects ◽  
Intact Cells ◽  
Imp Dehydrogenase

A rapid and convenient method has been developed to monitor the inhibition of inosinate (IMP) dehydrogenase by antimetabolites in intact human CEM lymphocytes. This method is based on the determination of 3H release from [2,8-3H]hypoxanthine ([2,8-3H]Hx) or [2,8-3H]inosine ([2,8-3H]Ino). The validity of this procedure was assessed by evaluating IMP dehydrogenase inhibition in intact CEM cells by the well-known IMP dehydrogenase inhibitors ribavirin, mycophenolic acid and tiazofurin. As reference materials, several compounds that are targeted at other enzymes in de novo purine nucleotide anabolism (i.e. hadacidine, acivicin) or catabolism (i.e. 8-aminoguanosine, allopurinol) were evaluated. There was a strong correlation between the inhibitory effects of the IMP dehydrogenase inhibitors (ribavirin, mycophenolic acid, tiazofurin) on 3H release from [2,8-3H]Hx and [2,8-3H]Ino in intact CEM cells and their ability to decrease intracellular GTP pool levels. The other compounds (hadacidine, acivicin, 8-aminoguanosine, allopurinol) had no marked effect on 3H release from [2,8-3H]Hx. Using this method, we demonstrated that the novel ribavirin analogue, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide, is a potent inhibitor of IMP dehydrogenase in intact cells.

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

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 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

Metabolism and disposition of the novel antileukaemic drug, benzamide riboside, in the isolated perfused rat liver

Life Sciences ◽  
2001 ◽  
Vol 69 (21) ◽  
pp. 2489-2502 ◽  
Author(s):  
Alexandra Salamon ◽  
Birgit Hagenauer ◽  
Therese Thalhammer ◽  
Thomas Szekeres ◽  
Karsten Krohn ◽  
...  
Keyword(s):  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
The Novel ◽  
Perfused Rat Liver ◽  
Benzamide Riboside

The novel steroidal glycoside from the dried bulb of Allium Macrostemon Bunge inhibits platelet activation

2010 ◽  
Vol 34 (8) ◽  
pp. S33-S33
Author(s):  
Wenchao Ou ◽  
Haifeng Chen ◽  
Yun Zhong ◽  
Benrong Liu ◽  
Keji Chen
Keyword(s):  
Platelet Activation ◽  
The Novel ◽  
Steroidal Glycoside ◽  
Allium Macrostemon
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