Protease Inhibitors: Innovation Drives Drug Pipeline

Table of Contents

• INTRODUCTION TO THE WORLD OF PROTEASES
• 1.1. What Is a Protease?
• Proteases, Proteinases, Exopeptidases, and Endopeptidases
• Proteolytic Cascades
• 1.2. The Renin-Angiotensin-Aldosterone System - RAAS
• 1.3. Coagulation Cascade
• 1.4. Multiplicity of Potential Drug Targets

• OVERVIEW OF PROTEASE TARGET CLASSES
• 2.1. Overview
• 2.2. Classification
• 2.3. Aspartic Proteases
• A01 Family
• A22 Subfamily
• 2.4. Serine Proteases
• S01 Proteases
• Coagulation Factors
• Kallikreins
• Complement and uPA
• Trypsin and Chymotrypsin
• Tryptase and Elastase
• Other S01 Serine Proteases
• Heat Shock Proteins
• Dipeptidyl-Peptidases
• Other Serine Proteases
• 2.5. Threonine Proteases
• 2.6. Cysteine Proteases
• Caspases
• Cathepsins
• Calpains
• Ubiquitin-Specific Peptidases
• Other Cysteine Proteases
• 2.7. Metalloproteases
• Aminopeptidases
• Carboxypeptidase
• Endopeptidases
• Matrix Metalloproteases
• ADAM Family
• ADAM-TS Family
• Other Metalloproteases
• 2.8. Non-mammalian Proteases
• Bacterial Proteases
• Viral Proteases
• Parasitic Proteases

• PROTEASES AS DRUG TARGETS
• 3.1. Introduction
• 3.2. Target Distribution
• 3.3. Protease Structures
• 3.4. Mechanism of Inhibition
• 3.5. Screening Issues
• 3.6. Summary

• Protease Inhibitor Drugs
• 4.1. Overview
• 4.2. ACE Inhibitors
• 4.3. HIV Protease Inhibitors
• 4.4. Emerging Protease Inhibitors
• Sitagliptin
• Vildagliptin
• Aliskerin

• PROTEASE INHIBITORS IN CLINICAL DEVELOPMENT
• 5.1. Overview
• 5.2. By Company
• 5.3. By Indication
• Cardiovascular Disease
• Renin Inhibitors
  • MK-8141
  • SPP-635
• Coagulation Cascade
• Factor Xa Inhibitors
  • Rivaroxaban
  • Apixaban
• Indirect Factor Xa Inhibitors
  • Idraparinux
  • Idrabiotaparinux
  • Octaparine
  • M-enoxaparin and M-118
• Direct Factor Xa Inhibitors in Phase II
  • Otamixaban
  • YM-510
  • DU-1766
  • Eribaxaban
  • Betrixaban (PRT-054021)
  • TAK-442
  • LY-517717
• Thrombin Inhibitors
  • Dabigatran
  • AZD-0837
• Thrombin Inhibitors in Phase II
• Other Peptidase Inhibitors
  • LCZ-696
  • Daglutril
  • TPC-806
  • TTP-889
• Metabolic Diseases
• DPP IV Inhibitors
  • Alogliptin
  • Saxagliptin
  • Linagliptin
  • Dutogliptin
• DPP IV Inhibitors in Phase II
  • PF-734200
  • Melogliptin (GRC-8200)
  • TA-6666 & MP-51
  • AMG-222
  • SYR-472 & SYR-619
  • KRP-104 & LC-15-0444
  • Carmegliptin
• CNS Diseases
• General Protease Inhibitors
  • SLV-334
  • DP-b99
• Beta-Secretase (BACE1) Inhibitors
• Gamma-Secretase Inhibitors
  • NIC5-15
  • Semagacestat
  • Tarenflurbil
• Caspase Inhibitors
• Inflammatory and Musculoskeletal Diseases
• COPD
  • Elastase Inhibitors
    • Depelestat
    • AZD-9668 & BAY 71-9678
  • MMP-12 Inhibitors
• Rheumatoid Arthritis
  • Cathepsin S Inhibitors
• Osteoarthritis
  • Aggrecanase Inhibitors
• Allergic Diseases
• Chymase and Tryptase Inhibitors
• MMP-9 Inhibitors
• Osteoporosis
• Cathepsin K Inhibitors
  • Odanacatib
  • ONO-5334
  • MIV-701
  • VEL-0230
• Oncology
• Protease and Metalloprotease Inhibitors
  • Tigapotide
  • Aderbasib
  • XL-784
  • R-4733
• Viral Infections
• Hepatitis C
  • NS3 Protease Inhibitors
    • Ciluprevir
    • ITMN-191
    • ACH-1625
    • IDX-136 & IDX-316
    • TMC-435350
    • MK-7009
    • Telaprevir
    • VX-500 & VX-813
    • Boceprevir
  • Caspase Inhibitors
    • LB-84451
    • Emricasan
    • EP-1013
    • CTS-1027
• HIV
  • HIV Protease Inhibitors
    • MK-8122
    • SPI-256
    • DG-17
• Bacterial and Parasitic Infections
• 5.4. Outlook

• COMPANY PROFILES
• 6.1. Introduction
• Major Companies
• AstraZeneca
• Bayer
• Boehringer Ingelheim
• Bristol-Myers Squibb
• Eli Lilly
• Merck
• Novartis
• Pfizer
• Roche
• sanofi-aventis
• Schering Plough
• Takeda
• 6.2. Selected Biotechnology Companies
• Ambrilia Biopharma
• Amura Therapeutics
• Idenix Pharmaceuticals
• Incyte
• Medivir AB
• Sequoia Pharmaceuticals
• Speedel Holding AG
• Velcura Therapeutics
• Vertex Pharmaceuticals
• Virobay

• NEAR-TERM COMMERCIAL PROSPECTS
• 7.1. Introduction
• 7.2. Cardiovascular Diseases
• 7.3. Diabetes
• 7.4. Other Indications
• 7.5. Conclusions

• EXPERT INTERVIEWS
• 8.1. Mark Whittaker PhD, Senior Vice President Drug Discovery, Evotec OAI, Abingdon, UK, and Scientific Director of Evotec' s Services Divisions
• 8.2. Professor Bertil Samuelsson PhD, Vice President, Research, Medivir AB, Huddinge, Sweden

• Company Index with Web Addresses