Chapter 1: Executive Summary
Chapter 2: Introduction
Membrane Receptor Pathways
Mitogen-Activated Protein Kinase Pathways
Extracellular Signal-Related Kinase (ERK) Pathway
Stress Activated Protein Kinase (SAPK) Pathway
P38 MAPK Pathway
G-Protein Coupled Receptors
PI3K/Akt Signalling
Jak/STAT Signalling
NF-êB Signalling
Insulin Signalling
B Cells and T Cells
Nuclear Receptors
Nuclear Receptor Structure
Nuclear Receptors as Pharmaceutical Targets
Chapter 3: Cancer
Market for Novel Therapies
Cell Cycle Control
Manipulation of the Cell Cycle to Enhance the Therapeutic Window
Mechanism-Based Protection of Normal Cells
p53-Dependent Checkpoints
Growth Factor Activated Pathways
CDK Inhibitors
Cyclin-Dependent Kinase Modulators in Clinical Development
Flavopiridol
Trastuzumab and Flavopiridol
Epothilone B and Flavopiridol
Imatinib and Flavopiridol
UCN-01
Molecular Targets for Cancer Drug Development
Bcl-2
Bcr/Abl
Cyclo-oxygenase
The ErbB Family
ErbB2
Epidermal Growth Factor Receptor
Farnesyl Transferase
FLT3
Heat Shock Protein 90
Kit
Mammalian Target of Rapamycin (mTOR)
Mitogen Activated ERK Kinase (MEK)
Proteasome
Protein Kinase C
Raf-1 Kinase
Src Protein Kinase
Vascular Endothelial Growth Factor
Signal Transduction Modulators in Clinical Development for Cancer
Critical Aspects of Clinical Trial Design
17-AAG
Affinitak™
AP23573
AP23464
ARRY-142886
AZD3409
BAY 43-9006
Bevacizumab (Avastin™)
Bortezomib (Velcade™)
CCI-779
Celecoxib (Celebrex®)
CEP-701
CEP-7055
CI-1033
CI-1040
EKB-569
EMD72000
Erlotinib HCl
Gefitinib
GW572016
Imatinib Mesylate
Lonafarnib (Sarasar™)
MLN518
Oblimersen (Genasense™)
OSI-461
Pertuzumab(Omnitarg™)
PKC-412
RAD001
SU11248
Tipifarnib (Zarnestra®)
Trastuzumab (Herceptin®)
Vatalanib (PTK787)
VEGF Trap
ZD6474
Nuclear Receptors Targets for Cancer Therapy
Androgen Receptor
Estrogen Receptor (ER)
Progesterone Receptor (PR)
Nuclear Receptor Modulators as Cancer Therapeutics
Selective Estrogen Receptor Modulators (SERMS)
Aromatase Inhibitors
Fulvestrant (Faslodex®)
Signal Transduction Inhibitors and Endocrine Therapy
Prostate Cancer: Targeting the Androgen Receptor
Flavonoids and AR Activity
Proteasome Activity and AR Function
Nuclear Receptors as Targets for Chemoprevention
Vitamin D Receptor (VDR)
Retinoic Acid Receptors (RAR and RXR)
Retinoids in Chemoprevention
Chapter 4: Inflammatory/Autoimmune Disease
Molecular Targets for Anti-Inflammatory Drugs
Chemokines
Cyclooxygenase
Glucagon-like Peptide 2
Glucocorticoid Receptor (GR)
Glucocorticoid Receptor and Rheumatoid Arthritis
Intercellular Adhesion Molecule 1
Interleukin-1
Retinoid-Related Orphan Receptor á (RORá) and Inflammation
Tumor Necrosis Factor
Rheumatoid Arthritis
Signal Transduction Modulators in Development for Rheumatoid Arthritis
Adalimumab (Humira®)
Anakinra (Kineret®)
Belimumab (LymphoStat-B™)
CTLA4Ig (Abatacept)
Etanercept (Enbrel®)
IL-1 Trap
Infliximab (Remicade®)
ISIS 104838
MLN1202
PRO70769
Rituximab (Rituxan®)
Inflammatory Bowel Disease
Signal Transduction Modulators in Clinical Development for Inflammatory
Bowel Diseases
ALX-0600 (Teduglutide)
Alicaforsen (ISIS2302)
Adalimumab (Humira®)
CDP-870
CNI-1493 (Semapimod)
Traficet-EN™
Multiple Sclerosis
Targeted Drug Candidates in Development for MS
MBP8298
NBI-5788
Chapter 5: Metabolic Syndrome
Molecular Targets for Drugs to Treat Metabolic Syndrome
â3-Adrenoceptor
Glucagon-Like Peptide 1
Leptin
Peroxisome Proliferator Activated Receptor (PPAR)
PPARä
Protein Kinase C-â
Protein Tyrosine-Phosphatase 1B
Diabetes (Type 2)
Anti-Diabetic Drugs in Clinical Development
Balaglitazone
CJC-1131 (DAC-GLP-1)
Exenatide (exendin-4)
ISIS 113715
LAF 237
Liraglutide (NN2211)
LY333531 (Ruboxistaurin)
LY818
LY929
MBX-102
Muraglitazar
Pioglitazone (Actos®)
Rosiglitazone (Avandia®)
T131
Tesaglitazar (Galida™)
Obesity
Anti-Obesity Drugs in Clinical Development
Acomplia™ (rimonabant)
AOD9604
Axokine®
PYY 3-36 Nasal Formulation
T71
Chapter 6: Company Profiles
Abbott Laboratories
Amylin Pharmaceuticals
Ariad Pharmaceuticals
Array BioPharma
AstraZeneca
Aventis
Bayer
BioMS Medical
Bristol-Myers Squibb
CellTech
Cephalon
ChemoCentryx
ConjuChem
Eli Lilly
EMD Pharmaceuticals
Genentech
Genta
GlaxoSmithKline
Human Genome Sciences
Ilex Oncology
Isis Pharmaceuticals
Johnson and Johnson
Ligand Pharmaceuticals
Metabolex
Metabolic Pharmaceuticals
Millennium
Nastech Pharmaceutical Company
Neurocrine Biosciences
Novartis
Novo Nordisk
NPS Pharmaceuticals
Onyx
OSI Pharmaceuticals
Pfizer
Regeneron
Sanofi-Synthelabo
Schering Plough
Tularik
Wyeth
Chapter 7: Concluding Remarks
Promising Cancer Drug Candidates
Promising Drug Candidates for Inflammatory and Autoimmune Diseases
Promising Drug Candidates for Metabolic Syndrome
