Methods in enzymology / edited by Kevan M. Shokat
|出版者||(Waltham, Massachusetts : Academic Press)|
|大きさ||1 online resource (296 pages, 42 unnumbered pages of plates) : illustrations (some color)|
|一般注記|| Includes bibliographical references at the end of each chapters and index.
Online resource; title from PDF title page (ebrary, viewed December 12, 2014).
Front Cover; Protein Kinase Inhibitors in Research and Medicine ; Copyright; Contents; Contributors; Preface; Chapter One: Catalytic Mechanisms and Regulation of Protein Kinases; 1. Introduction; 2. Kinetic Mechanism; 3. Chemical Mechanism of Kinase Phosphoryl Transfer; 4. Applications of Mechanistic Studies in Understanding Kinase Function and Regulation; 4.1. Bisubstrate analogs; 4.2. Oncogenic kinase mutants; 4.3. Chemical rescue of tyrosine kinases; 5. Summary and Outlook; References; Chapter Two: A Structural Atlas of Kinases Inhibited by Clinically Approved Drugs; 1. Introduction
2. Kinase Structure and Catalytic Mechanism3. Staurosporine: A Promiscuous ATP-Competitive Inhibitor; 4. BCR-Abl Inhibitors; 4.1. Imatinib binds to a ``DFG-out ́ ́ Abl conformation; 4.2. Nilotinib (Tasigna): An imatinib analog effective against several imatinib-resistant Abl variants; 4.3. Ponatinib (Iclusig) overcomes an Abl gatekeeper resistance mutation; 4.4. Bosutinib (Bosulif) inhibits BCR-Abl; 4.5. Dasatinib (Sprycel) binds to a ``DFG-in ́ ́ conformation of Abl; 5. Tofacitinib (Xeljanz) Binds to a ``DFG-in ́ ́ Conformation of Janus Kinase; 6. Inhibition of Receptor Tyrosine Kinases
6.1. Imatinib binds to a ``DFG-out ́ ́ conformation of c-Kit6.2. Inhibitors of vascular endothelial growth factor receptor; 6.3. Crizotinib (Xalkori) binds a ``DFG-in ́ ́ conformation of ALK and c-MET; 6.4. Gefitinib (Iressa) and erlotinib (Tarceva) inhibit EGFR; 6.5. Development of a more selective EGFR inhibitor: Lapatinib (Tykerb); 6.6. Afatinib (Gilotrif): A selective kinase inhibitor that reacts covalently; 6.7. Vandetanib (Caprelsa): A quinazoline analog that inhibits RET; 7. Vemurafenib (Zelboraf) Binds to A ``DFG-in ́ ́ Conformation in the Ser/Thr Kinase RAF
8. Inhibitors That Occupy Pockets Other Than the ATP-Binding Site8.1. Benzothiazines bind an allosteric site in focal adhesion kinase; 8.2. PD318088 binds to MEK noncompetitively with ATP; 8.3. Inhibitors that bind to the kinase domain to disrupt substrate recruitment; 9. Summary; Acknowledgments; References; Chapter Three: Fragment-Based Approaches to the Discovery of Kinase Inhibitors; 1. Introduction; 1.1. Challenges of kinases as drug targets; 2. Fragment-Based Drug Discovery; 2.1. Advantages of FBDD; 2.2. Challenges of FBDD; 2.3. Discovering kinase inhibitors with FBDD
2.4. FBDD-derived kinase inhibitors in the clinic3. Identifying Fragment Hits; 3.1. Library construction; 3.2. Hit identification; 3.3. Hit validation; 4. From Fragments to Leads; 4.1. Selection of hits for optimization; 4.2. Structure-guided optimization; 4.3. Achieving selective inhibition; 5. Alternative Inhibition Strategies; 5.1. Type II inhibition; 5.2. Type III inhibition; 5.3. Other modes of inhibition; 6. Summary; Acknowledgments; References; Chapter Four: Targeting Protein Kinases with Selective and Semipromiscuous Covalent Inhibitors; 1. Introduction
This new volume of Methods in Enzymology continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers protein kinase inhibitors in research and medicine, and includes chapters on such topics as fragment-based screening, broad kinome profiling of kinase inhibitors, and designing drug-resistant kinase alleles. Continues the legacy of this premier serial with quality chapters authored by leaders in the field Covers research methods in biomineralization scienceContains sections focusing on protein kinase inhibitors in research and medicine.
Elsevier ScienceDirect Book Series Package - Methods in Enzymology (2000-ongoing)
|著者標目||Shokat, Kevan M. editor|
|件 名||LCSH:Protein kinases -- Inhibitors
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