Chapter 1: Executive Summary
Chapter 2: Introduction and Background on Phosphatases
PTP Super-family
Chapter 3: Phosphatases in Signal Transduction
Classification of Phosphatases
Serine and ThreonineSpecific Phosphatases
PP1 and PP2A
PP2B
PP2C
Protein Tyrosine Phosphatases (PTP)
PTPs in Signaling
PTP-1B
Phosphatases in Insulin Receptor Signaling
LAR
RPTPs
Other Phosphatases
RPTPa
SH2 Phosphatases: SHP-1, SHP-2
RPTPe
TCPTP
HePTP
Chapter 4: Phosphatases Associated with Disease
Protein Tyrosine Phosphatase (PTP) in the Immune System
PTP in Infectious Diseases
PTP in Vascular Leakage
PTP in Osteoporosis
Phosphatases in Apoptosis
BCL-2 Family Proteins
Phosphatases in Cancer
PTEN
MAPK
Phosphatases in Diabetes and Obesity
PRL-3
CDC25
MKP-1
PP2A
PTP1B in Diabetes and Obesity
Phosphatases in Alzheimer’s Disease
Small Molecule Inhibitors of Serine/Threonine Protein Phosphatases
Cantharidin
Biological Effects
Modifications Anhydride
Multiple Modifications
Involvement of PTPs in Control of Receptor Tyrosine Kinase Signaling
Chapter 5: Commercial Opportunity and Legal Aspects of
Commercialization
Structural Challenges in Developing Anti-PTP Molecules
Chapter 6: Literature and Latest News on Phosphatases
Literature Bibliography
Latest News in Phosphatases Area
Sunesis Identifies New Small Molecules to Target PTP-1B
ISIS Pharmaceuticals
Chapter 7: Intellectual Property Landscape for Phosphatases
and Their Inhibitors
Chapter 8: Companies Providing Reagents and Assays for
Phosphatase Space
Commercial Opportunities
Chapter 9: Interviews with Industry Experts
Dr. Rob Hooft, Principal Scientist / Project Leader, Serono
Research Institute
Paul G. Abrams, MD, JD, President & Chief Executive Officer, CEPTYR 9-3
James Wells, Ph.D., President, Chief Officer and Founder, Sunesis Scientific
Pharmaceuticals Inc
Christopher Lipinski, Ph.D., Adjunct Senior Research Fellow,
PFIZER Global R&D, Groton Labs
Chapter 10: Company Profiles
Ceptyr
Isis Pharmaceuticals, Inc
Serono Pharmaceuticals
Sunesis Pharmaceuticals, Inc.
Vertex Pharmaceutical Inc
TABLE OF E XHIBITS
Exhibit 1.1 Number of Publications on Phosphatases in the Last Five Decades
Exhibit 1.2 Overview of PTPs that are Potential Therapeutic Targets, Grouped
by Disease Area
Exhibit 1.3 Companies Developing Therapeutic Molecules Targeting Phosphatases
Exhibit 2.1 The Reversible Events in Phosphorylation and Dephosphorylation by
Kinase and Phosphatase
Exhibit 2.2 Classification of
Exhibit 2.3 Structural Classification of Phosphatases
Exhibit 3.1 Role of Phosphatases in Insulin Signaling
Exhibit 3.2 Insulin Mediated Signal Transduction
Exhibit 3.3 Number of PTP Family Genes Predicted from Celera and
Human Genome Sequences, Based on Carious PTP Subclasses
Exhibit 4.1 Phosphorylation and Dephosphorylation Events of Proteins
Related to Apoptosis
Exhibit 4.2 Inhibition of Serine/Threonine Protein Phosphatases 1 and 2A by
Various Natural Toxins (IC50 nM)
Exhibit 5.1 Protein Target Depicted from Human Genome Sequencing
Exhibit 5.2 Schematic of Segmentation of Number of Human Drug Targets
Depicted from Human Genome Sequencing
Exhibit 5.3 Schematic of Signal Transduction Pathway Showing the Involvement
of Phosphate Addition and Removal (Potential Role of Kinase
and Phosphatase)
Exhibit 5.4 Human Protein Substrates and Associated Phosphatases
Exhibit Identified Related to Phosphatases 5.5 Number and Classes of Structures
Exhibit 5.6 Companies Involved in Protein Tyrosine Phosphatase-1B Inhibitor Discovery
Exhibit 5.7 Development of Small Molecules to Target Phosphatases Proteins
