Inhibitors of Cyclin-dependent Kinases as Anti-tumor Agents

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Overview

One of the few books to cover all aspects of cyclin-dependent kinases (CDKs), Inhibitors of Cyclin-dependent Kinases as Anti-tumor Agents provides an overview of CDKs as molecular and functional entities, their involvement in different disease processes, and their potential for pharmacological modulation. With contributions from the top international researchers in the field, the book takes a contemporary approach to study the importance of rational drug design and knowledge-based therapeutics in relation to CDKs.

The first two sections of the book discuss the integration of cell cycle control pathways, opportunities for targeting, targets of inhibitors, and the evaluation of CDK inhibitors, exploring topics such as the in vivo function of CDKs in normal homeostasisand tumor development and the structural biology of CDKs. The third section examines the design, development, and chemistry of small molecule CDK inhibitors, with discussions ranging from the early-stage discovery of new chemical entities with a capacity to inhibit CDKs to late-stage compounds in clinical development. The final section assesses the current status of CDK inhibitors in clinical trials, the therapeutic deployment challenges of small molecule inhibitors, and the future development of CDK inhibitors as anticancer agents.

The field of drug development is at a critical point in terms of understanding the availability, advantages, and drawbacks of CDKs as therapeutic targets for small molecules. Providing the most up-to-date, in-depth coverage available in a single volume, Inhibitors of Cyclin-dependent Kinases as Anti-tumor Agents surveys the success of the agents developed thus far, the possibility of new routes to more selective inhibitors, and the growing appreciation of critical, therapeutic issues.

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Editorial Reviews

Doody's Review Service
Reviewer: Sara A Li, PhD (University of Kansas Medical Center)
Description: This monograph in the CRC Enzyme Inhibitors Series provides an excellent review of the current status in the development of cyclin-dependent kinases (CDK) inhibitors.
Purpose: The purpose is to review the current status of the development of CDK inhibitors.
Audience: Basic and clinical scientists interested in the development of new cancer therapies are the intended audience. The book will be particularly useful for scientists interested in translational research. The authors of the chapters are experts in their fields of research.
Features: The book is divided into four sections to allow readers to become familiar with possible targets of cell cycle inhibitions. The initial chapters provide an excellent background on the role of CDK in cell cycle control pathways and open the doors for the understanding of their potential use as therapeutic agents. The subsequent chapters review the use of mammalian systems, their selective inhibition, detailed description of their design, development, and chemistry. In addition, the book includes a summary of their current use in combination with other neoplastic agents and a perspective for their future use.
Assessment: This excellent monograph provides basic, clinical, and translational information on the potential use of CDK inhibitors as anti-tumor agents.
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Product Details

  • ISBN-13: 9780849337741
  • Publisher: CRC Press
  • Publication date: 8/26/2006
  • Series: Enzyme Inhibitors Series
  • Pages: 448
  • Product dimensions: 6.10 (w) x 9.10 (h) x 1.20 (d)

Table of Contents

INTEGRATION OF CELL CYCLE CONTROL PATHWAYS AND THE OPPORTUNITIES FOR TARGETING
Cell Cycle Dynamics and the Challenges for CDK Targeting
Paul J. Smith, Emeline Furon, and Rachel J. Errington
Functional Regulation of CIP/KIP CDK Inhibitors
Mong-Hong Lee and Ruiying Zhao
Mouse Models to Study the In Vivo Function of Cyclin-Dependent Kinases in Normal Homeostasis and Tumor Development
Marcos Malumbres, Pierre Dubus, and Sagrario Ortega
Cyclin-Dependent Kinase Inhibitors and Vascular Disease
Martin F. Crook and Manfred Boehm
CDK INHIBITORS: TARGETS AND THEIR EVALUATION
Evaluation of CDK Inhibitor Selectivity: From Affinity Chromatography to Yeast Genetics
Stéphane Bach, Marc Blondel, and Laurent Meijer
Development of CDK Inhibitors as Anticancer Agents: From Rational Design to CDK4-Specific Inhibition
Sachin Mahale and Bhabatosh Chaudhuri
Three-Dimensional Structures of Cyclin-Dependent Kinases and Their Inhibitor Complexes
Ursula Schulze-Gahmen and Sung-Hou Kim
CDK INHIBITORS: CHEMISTRY FOCUS
Cyclin-Dependent Kinase Small Molecule Modulators for Cancer Therapy
Adrian M. Senderowicz
(R)-Roscovitine (CYC202, Seliciclib)
Laurent Meijer, Karima Bettayeb, and Hervé Galons
Development, Selectivity, and Application of Paullones, a Family of CDK Inhibitors
Conrad Kunick, Thomas Lemcke, and Laurent Meijer
Discovery of BMS-387032, a Potent Cyclin-Dependent Kinase Inhibitor in Clinical Development
John T. Hunt
Oxindole Inhibitors of Cyclin-Dependent Kinases as Antitumor Agents
Philip A. Harris
Indenopyrazoles as Cyclin-Dependent Kinase Inhibitors
David J. Carini, Catherine R. Burton, and Steven P. Seitz
Development of Indolocarbazoles as Cyclin D1/CDK4 Inhibitors
Guoxin Zhu
Pyrazoles as Efficient Adenine-Mimetic Heterocycles for the Discovery of CDK Inhibitors
Paolo Pevarello and Anna Vulpetti
Pyrazolo [3,4-d] pyrimidin-4-ones: Exploring the Structural Determinants of Potency and Selectivity in Cyclin-Dependent Kinase Inhibition
Jay A. Markwalder and Steven P. Seitz
THERAPEUTIC PERSPECTIVE
Cyclin-Dependent Kinase Inhibitors and Combination Therapy: Experimental and Clinical Status
Lloyd R. Kelland
CDK Inhibitors as Anticancer Agents: Perspectives for the Future
Jayalakshmi Sridhar, Nagarajan Pattabiraman, Eliot M. Rosen,
and Richard G. Pestell
INDEX

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