Target Validation in Drug Discovery

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 serve as the focus of the final section of the book.

I: Pharmaceutical biotechnology for target validation

Chapter 1: GENERATION OF TRANSGENIC ANIMALS

Chapter 2: TARGET VALIDATION IN CHEMOGENOMICS

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

Chapter 4: MONOCLONAL ANTIBODY TO HER-2 IN BREAST CANCER

Chapter 5: VALIDATION OF TNF AS A DRUG TARGET IN INFLAMMATORY BOWEL DISEASE

Chapter 6: ANTI-CCL-2/MCP-1: DIRECTED BIOLOGICALS FOR INFLAMMATORY AND MALIGNANT DISEASES

Chapter 7: TARGETING IL-12P40 FOR IMMUNE-MEDIATED DISEASE

Chapter 8: THE GPIIB/IIIA ANTAGONIST ABCIXIMAB FOR ACUTE PERCUTANEOUS CORONARY INTERVENTION

III: Validating targets of small molecule approaches

Chapter 9: EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) INHIBITOR FOR ONCOLOGY: DISCOVERY AND DEVELOPMENT OF ERLOTINIB

Chapter 10: PROGRESS IN ACHIEVING PROOF OF CONCEPT FOR p38 KINASE INHIBITORS

Chapter 11: IKK-2/NF-κB-DEPENDENT TRANSCRIPTION

Chapter 12: TNF SIGNALING PATHWAY INHIBITORS FOR INFLAMMATION-CCR2 ANTAGONISTS

Chapter 13: THE DISCOVERY OF ELTROMBOPAG, AN ORALLY BIOAVAILABLE TpoR AGONIST

Chapter 14: ORALLY BIOAVAILABLE GLYCOPROTEIN IIB/IIIA ANTAGONISTS: A NEGATIVE CASE STUDY

INDEX