1st Edition

Inhibitors of Cyclin-dependent Kinases as Anti-tumor Agents

Edited By Paul J. Smith, Eddy W. Yue Copyright 2007
    8 Color & 106 B/W Illustrations
    by CRC Press

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    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.

    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
    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
    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
    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


    Paul J. Smith, Eddy W. Yue

    "Smith and Yue have done an admirable job with this volume. There is a clear logic in the arrangement of the chapters. The introductory chapter is well suited to readers who are not familiar with this particular topic. Jargon is kept to a bar minimum . . . This highly readable volume should serve to get newcomers to the field up to speed quite quickly."

    – D. Eric Walters, Department of Biochemistry and Molecular Biology, Rosalind Franklin University of Medicine, in Journal of Medicinal Chemistry, 2007, Vol. 50, No. 19

    "Providing up-to-date, in-depth coverage 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."

    – In Anticancer Research, Sept/ Oct 2007, Vol. 27, No. 5A