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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.
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
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