Cancer drug design and discovery / Stephen Neidle.

Format:

Book

Author/Creator:

Neidle, Stephen.

Language:

English

Subjects (All):

Antineoplastic agents--Development.

Antineoplastic agents.

Antineoplastic agents--Design.

Physical Description:

1 online resource (517 pages)

Edition:

1st ed.

Place of Publication:

London : Academic, c2008.

Language Note:

English

Summary:

The ultimate source of information on the design of new anticancer agents, emphasizing small molecules, this newest work covers recent notable successes resulting from the human genome and cancer genomics projects. These advances have provided information on targets involved in specific cancers that are leading to effective medicines for at least some of the common solid tumors. Unique sections explain the basic underlying principles of cancer drug development and provide a practical introduction to modern methods of drug design.

Contents:

Front Cover; Cancer Drug Design and Discovery; Copyright Page; Contents; About the editor; Contributors; Introduction; PART I: BASIC PRINCIPLES; Chapter 1 Modern cancer drug discovery: integrating targets, technologies and treatments; 1.1 Introduction: changing times; 1.2 Successes and limitations; 1.3 Integrated small-molecule drug discovery and development; 1.4 New molecular targets: the ""druggable"" cancer genome; 1.5 From drug target to development candidate; 1.6 Examples of case histories for molecularly targeted cancer therapeutics

1.7 Biomarkers, the pharmacological audit trail and clinical development; 1.8 Conclusions and outlook: towards individualized molecular cancer medicine; References; Chapter 2 Preclinical pharmacology and in vivo models; 2.1 Introduction; 2.2 Contemporary preclinical cancer drug discovery; 2.3 In vitro pharmacological evaluation; 2.4 Information gained from in vitro cell lines; 2.5 In vivo pharmacokinetics (PK) and pharmacodynamics (PD): continuing the pharmacological audit trail; 2.6 In vivo anti-tumor models: choice and predictiveness?; 2.7 Concluding remarks; References

Chapter 3 Clinical trial designs for more rapid proof-of-principle and approval; 3.1 Introduction; 3.2 NDA plan at the time of IND; 3.3 Phase I trial design innovations; 3.4 Concept of a continuous Phase I; 3.5 Phase II trial design innovations; 3.6 Phase III trial design innovations (enrichment designs); 3.7 Other approaches to enrich trial populations; 3.8 Innovations in design and selection of endpoints; 3.9 Regulatory strategies; 3.10 Other approaches to accelerate drug development; 3.11 New perspectives; 3.12 Summary; References; PART II: METHODOLOGY

Chapter 4 Structural biology and anticancer drug design; 4.1 Introduction; 4.2 High-throughput X-ray crystallography; 4.3 Structural biology and structure-based drug design; 4.4 Fragment screening using X-ray crystallography; 4.5 Case history: cyclin-dependent kinase inhibitors, from fragment hit to clinical candidate; 4.6 Compound profiling; 4.7 Conclusions; References; Chapter 5 Natural product chemistry and anticancer drug discovery; 5.1 Introduction; 5.2 Exemestane (aromasin); 5.3 Fulvestrant/faslodex; 5.4 Flavonoids; 5.5 Bexarotene (targretin); 5.6 Epothilones; 5.7 Maytansine

5.8 Geldanamycin; 5.9 UCN-01; 5.10 Camptothecin; 5.11 Prodigiosin; 5.12 Azacitidine; 5.13 FK-288; 5.14 Hemiasterlin; 5.15 Calicheamicin; 5.16 Conclusion; References; Chapter 6 Pharmacokinetics and ADME optimization in drug discovery; 6.1 Introduction; 6.2 Absorption; 6.3 Distribution; 6.4 Metabolism; 6.5 Elimination; 6.6 Biochemical barriers to drug therapy: efflux transporters; 6.7 Induction; 6.8 Conclusions; References; PART III: DRUGS IN THE CLINIC; Chapter 7 Temozolomide: from cytotoxic to molecularly-targeted agent; 7.1 Introduction; 7.2 Towards imidazotetrazines and azolastone (mitozolomide)

Notes:

Description based upon print version of record.

Includes bibliographical references and index.

ISBN:

1-281-76368-3

9786611763688

0-08-055495-4

OCLC:

476216470