Target validation in drug discovery [[electronic resource] /] / Brian W. Metcalf and Susan Dillon, editors

• Record Nr.: UNINA9910784646803321
• Pubbl/distr/stampa: Boston, MA, : Academic Press, 2006
• ISBN: 1-280-70760-7; 9786610707607; 0-08-046597-8
• Descrizione fisica: 1 online resource (293 p.)
• Altri autori (Persone): MetcalfBrian W; DillonSusan <1952->
• Disciplina: 615/.19
• Soggetti: Drug development; Drugs - Testing; High throughput screening (Drug development)
• Lingua di pubblicazione: Inglese
• Formato: Materiale a stampa
• Livello bibliografico: Monografia
• Note generali: Description based upon print version of record.
• Nota di bibliografia: Includes bibliographical references and index.
• Nota di contenuto: Front Cover; Title Page; Copyright Page; Table of Contents; Preface; Contributors; PART I PHARMACEUTICAL BIOTECHNOLOGY FOR TARGET VALIDATION; Chapter 1 Generation of Transgenic Animals; I. INTRODUCTION; II. GENERATION OF TRANSGENIC ANIMALS FOR TARGET VALIDATION; III. CONCLUSION; ACKNOWLEDGMENTS; RECOMMENDED RESOURCES; REFERENCES; Chapter 2 Target Validation in Chemogenomics; I. INTRODUCTION; II. REVERSE CHEMOGENOMICS: TARGET VALIDATION USING COMPOUNDS WITH KNOWN MOLECULAR TARGET (AND/OR MECHANISM OF ACTION); III. FORWARD CHEMOGENOMICS: TARGET IDENTIFICATION/VALIDATION USING COMPOUNDS WITH UNKNOWN MECHANISM OF ACTIONIV. CONCLUSION; REFERENCES; PART II TARGET VALIDATION FOR BIOPHARMACEUTICAL DRUG DISCOVERY; Chapter 3 Cetuximab (Erbitux®), An Anti-Epidermal Growth Factor Receptor Antibody for the Treatment of Metastatic Colorectal Cancer; I. INTRODUCTION; II. EPIDERMAL GROWTH FACTOR RECEPTOR AND ITS ROLE IN HUMAN CANCER; III. CETUXIMAB (ERBITUX®, IMC-C225); IV. CETUXIMAB IN CLINICAL STUDIES IN PATIENTS WITH mCRC; V. MECHANISMS OF ; ACTION OF CETUXIMAB; VI. CONCLUSIONS AND PERSPECTIVES; RECOMMENDED RESOURCESREFERENCES; Chapter 4 Monoclonal Antibody to HER-2 in Breast Cancer; I. INTRODUCTION; II. MECHANISM OF ACTION OF TRASTUZUMAB; III. MOLECULAR MECHANISMS OF TRASTUZUMAB RESISTANCE; IV. ASSESSMENT OF HER-2 STATUS; V. CLINICAL TRIALS WITH TRASTUZUMAB; CONCLUSION; ACKNOWLEDGMENTS; USEFUL WEBSITES; REFERENCES; Chapter 5 Validation of TNF as a Drug Target in Inflammatory Bowel Disease; I. INTRODUCTION; II. TUMOR NECROSIS FACTOR; III. INFLAMMATORY BOWEL DISEASE; IV. PATHOPHYSIOLOGY OF IBD AND THE PUTATIVE ROLE OF TNF; V. CLINICAL EXPERIENCE WITH TNF-BLOCKING THERAPY IN IBD; CONCLUSIONACKNOWLEDGMENTS; REFERENCES; Chapter 6 Anti-CCL-2/MCP-1: Directed Biologicals for Inflammatory and Malignant Diseases; I. INTRODUCTION; II. IN VITRO ASSAYS TO ESTABLISH THE PRO-INFLAMMATORY ACTIVITIES OF CCL-2; III. IN VIVO VALIDATION STUDIES; IV. SUMMARY; ACKNOWLEDGMENTS; REFERENCES; Chapter 7 Targeting IL-12p40 for Immune-Mediated Disease; I. INTRODUCTION; II. IN VITRO TARGET VALIDATION OF IL-12p40; III. IN VIVO PROOF-OF-CONCEPT FOR IL-12p40 INHIBITION; IV. CONCLUSION; RECOMMENDED RESOURCES; REFERENCES; Chapter 8 The GPIIb/IIIa Antagonist Abciximab for Acute Percutaneous Coronary InterventionI. INTRODUCTION; II. RATIONALE FOR GPIIb/IIIa AS A TARGET IN CORONARY ARTERIAL DISEASE; III. GENERATION OF THE 7E3 MONOCLONAL ANTIBODY AGAINST GPIIb/IIIa; IV. IN VITRO STUDIES; V. ANIMAL STUDIES; VI. PLATELET PHARMACODYNAMIC PHENOMENA RECOGNIZED LATER; VII. CROSS REACTIVITY WITH OTHER INTEGRINS; VIII. INTEGRATION OF CLINICAL PHARMACOLOGY AND PRECLINICAL STUDIES; IX. CLINICAL STUDIES; X. CONCLUSION; RECOMMENDED RESOURCES; REFERENCES; PART III VALIDATING TARGETS OF SMALL MOLECULE APPROACHES; Chapter 9 Epidermal Growth Factor Receptor (EGFR) Inhibitor for Oncology: Discovery and Development of Erlotinib
• Sommario/riassunto: This work presents a comprehensive contemporary framework for approaching target validation in drug discovery. It begins with a detailed description of new enabling technologies, including aptamers, RNA interference, functional genomics, and proteomics. The next section looks at biologic drug development with in-depth discussion of lessons learned from such well-known cases as Erbitux, Herceptin, and Avastin. Additional targets known as ""second generation"" drugs, which can be identified when disease pathways are validated by biologics, present new possible small molecule therapeutics and