Protease Inhibitors: Innovation Drives Drug Pipeline

Published by: CHI Insight Pharma Reports

Published: Feb. 1, 2009 - 156 Pages

Table of Contents

Chapter 1

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

Chapter 2

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

Chapter 3

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

Chapter 4

Protease Inhibitor Drugs

4.1. Overview

4.2. ACE Inhibitors

4.3. HIV Protease Inhibitors

4.4. Emerging Protease Inhibitors

Sitagliptin

Vildagliptin

Aliskerin

Chapter 5

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

Chapter 6

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

Chapter 7

NEAR-TERM COMMERCIAL PROSPECTS

7.1. Introduction

7.2. Cardiovascular Diseases

7.3. Diabetes

7.4. Other Indications

7.5. Conclusions

Chapter 8

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

References

Company Index with Web Addresses

Tables and Figures

Figures:

Figure 1.1. Schematic of the Renin-Angiotensin-Aldosterone System

Figure 1.2. Schematic of the Coagulation Cascade

Figure 5.1. Development Status of Protease Inhibitors being Developed by Major Pharmaceutical Companies

Tables:

Table 2.1. Human Degradome by Catalytic Class

Table 2.2. A02 Family Aspartic Proteases

Table 2.3. A01 Family Aspartic Proteases

Table 2.4. A22 Family Aspartic Proteases

Table 2.5. S01 Serine Proteases that Affect the Coagulation Cascade

Table 2.6. S01 Kallikrein Serine Proteases

Table 2.7. S01 S01 Serine Proteases of the Complement System.

Table 2.8. S01 Trypsin-like Serine Proteases

Table 2.9. S01 Tryptase and Elastase-like Serine Proteases

Table 2.10. Other S01 Family Serine Proteases

Table 2.11. Sx2 Family Serine Proteases

Table 2.12. S09 Family Serine Proteases

Table 2.13. S08 Family Serine Proteases

Table 2.14. Serine Proteases from Other than the S01, Sx2, S08, and S09 Families

Table 2.15. Threonine Proteases

Table 2.16. Caspase Cysteine Proteases

Table 2.17. Cathepsin Cysteine Proteases

Table 2.18. Calpain Cysteine Proteases

Table 2.19. Ubiquitin Cysteine Proteases

Table 2.20. Non C01, C02, C14, and C19 Cysteine Proteases

Table 2.21. Aminopeptidase Metalloproteases

Table 2.22. Carboxypeptidase Metalloproteases

Table 2.23. Endopeptidase Metalloproteases

Table 2.24. Matrix Metalloproteases

Table 2.25. ADAM Family Metalloproteases

Table 2.26. ADAM-TS Family Metalloproteases

Table 2.27. M16, M19, M22, and M28 Family Metalloproteases

Table 2.28. Meta Zinc Metalloproteases

Table 4.1. Marketed ACE Inhibitors and 2007 Sales Revenues

Table 4.2. Marketed HIV Protease Inhibitors and 2007 Sales Revenues

Table 5.1. Protease Inhibitors in Development for Cardiovascular Diseases Other than Thrombosis

Table 5.2. Direct and Indirect Factor Xa Inhibitors in Development

Table 5.3. Thrombin Inhibitors in Development

Table 5.4. DPP-IV Inhibitors in Development

Table 5.5. Protease Inhibitors in Development for CNS Disorders

Table 5.6. Protease Inhibitors in Development for Inflammatory or Musculoskeletal Diseases

Table 5.7. Cathepsin K Inhibitors in Development

Table 5.8. Protease Inhibitors in Development for the Treatment of Cancer and Angiogenic Disorders

Table 5.9. Protease Inhibitors in Development for the Treatment of Viral Infections

Table 6.1. AstraZeneca's Protease Inhibitor Pipeline

Table 6.2. Bayer's Protease Inhibitor Pipeline

Table 6.3. Boehringer Ingelheim's Protease Inhibitor Pipeline

Table 6.4. Bristol-Myers Squibb's Protease Inhibitor Pipeline

Table 6.5. Eli Lilly's Protease Inhibitor Pipeline

Table 6.6. Merck's Protease Inhibitor Pipeline

Table 6.7. Novartis' Protease Inhibitor Pipeline

Table 6.8. Pfizer's Protease Inhibitor Pipeline

Table 6.9. Roche's Protease Inhibitor Pipeline

Table 6.10. sanofi-aventis' Protease Inhibitor Pipeline

Table 6.11. Schering Plough's Protease Inhibitor Pipeline

Table 6.12. Takeda's Protease Inhibitor Pipeline

Table 7.1. Protease Inhibitors in Late-stage Development and Anticipated NDA Filing Dates

Abstract

About MarketResearch.com
MarketResearch.com is an online aggregator selling over 300,000 market research reports, company profiles and country profiles from over 700 research firms. Our reports will provide you with the critical business and competitive intelligence you need for strategic planning and marketing research. Coverage includes the US, UK, Europe, Asia and global markets.