edited by
Krzysztof W. Pankiewicz
and Barry M. Goldstein

Inosine Monophosphate Dehydrogenase: A Major Therpeutic Target provides a comphrensive look at the chemotherapeutic inosine monophosphate deydrogenase. In addition to an overview of the field, this volume examines the molecular biology and gentics, the structure and mechanisms of IMPDH, inhibitor design, clinical applications, and new trends for the future.

Human IMPDH exists as two isoforms, type I and type II. Type I is expresses constitutively in normal cells, while type II is expressed predominantly in cancer cells and activated lymphocytes. Thus, the type II is a major target for the development of anticancer and immunosuppressive drugs.

Inosine Monophosphate Dehydrogenase: A Major Therapeutic Target provides a comprehensive look at the chemotherapeutic target inosine monophosphate dehydrogenase. This volume includes sections on molecular biology and genetics, structure and mechanism, and inhibitor design and clinical applications.

Contents

1. Inosine Monophosphate Dehydrogenase and Its Inhibitors: An Overview

Molecular Biology and Genetics

2. IMP, DH, and GTP: Linkage with Neoplasia, Target of Chemotherapy, Regulation of Ras, Signal Transduction, and Apoptosis
3. Biological Significance of Guanylate Synthesis and IMP Dehydrogenase Isoforms
4. An Emerging Cell Kinetics Regulation Network: Integrated Control of Nucleotide Metabolism and Cancer Gene Function
5. Targeted Disruption of the IMPDH: Type II Gene: Effect on Mouse Development and Lymphocyte Activation
6. Differential Splicing of Pneumocystis carinii Inosine 5'-Monophosphate Dehydrogenase mRNA: Implications for Producing Catalytically Active Protein

Structure and Mechanism

7. IMPDH Structure and Ligand Binding
8. Monovalent Cation Activation of IMP Dehydrogenase
9. IMP Dehydrogenase: Mechanism of Drug Selectivity
10. The Discovery of Thiazole-4-Carboxamide Adenine Dinucleotide (TAD) and a Recent Synthetic Approach for the Construction of a Hydrolytically Resistant Surrogate

Inhibitor Design and Clinical Applications

11. C-Nucleoside Analogs of Tiazofurin and Selenazofurin as Inosine 5'-Monophosphate Dehydrogenase Inhibitors
12. Studies with Benzamine Riboside, a Recent Inhibitor of Inosine 5'-Monophosphate Dehydrogenase
13. Cofactor Analogues as Inhibitors of IMP Dehydrogenase: Design and New Synthetic Approaches
14. Identification of Specific Inhibitors of IMP Dehydrogenase
15. Mizoribine: Experimental and Clinical Experience

Index

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