Length 156 pages

Date published February 2009

Print copies are available upon request. Call 781-972-5444. 

For Global Licenses, Multi-Reports Orders, Discounts or Order Questions.  

Dan Miller
Marketing Associate


Protease Inhibitors: Innovation Drives Drug Pipeline Overview


Cover ImageProtease Inhibitors: Innovation Drives Drug Pipeline

Author: Peter Norman, PhD, MBA




Proteases constitute one of the largest potential drug target enzyme families, with 647 human gene products incorporating protease sequences and mutated proteases having been identified.  In addition, there are many more proteases found in viruses, bacteria, and parasites, which are also potential drug targets. The therapeutic promise of protease inhibitors has been most clearly demonstrated by angiotensin-converting enzyme (ACE) and HIV drugs. 

Developments reviewed in this report indicate that more protease inhibitors, several having significant commercial potential, will reach the market over the next three to four years.  Examples are:

  • Oral antithrombotic agents to supplant warfarin
  • Novel renin-targeting hypertension candidates
  • Better-tolerated, oral, anti-hepatitis C agents 
  • Treatment of Alzheimer’s disease via γ-secretase
  • Cathepsin K inhibition for osteoporosis treatment
  • DPP IV inhibitors for managing type II diabetes

Inhibition of protease activity modulates physiological functions, either by reducing the formation of undesirable peptide mediators or by enhancing the beneficial effects of peptides by preventing their catabolism. A significant number of proteases have some potential as drug targets. Because of the disparate nature of the physiological roles of proteases and the diverse nature of their substrates, it has proved less straightforward to identify the number of human proteases that are potential drug targets in comparison to GPCRs or protein kinases. Proteases include drug targets for HIV and the clotting cascade as well as degradative enzymes such as elastase and dipeptidyl peptidases such as DPP IV.

Many viral, bacterial, and parasitic proteases are also potential drug targets and, due to their lower homology to their mammalian orthologs, offer target opportunities to identify selective inhibitors that have minimal cross-reactivity with mammalian proteases. In addition to these proteases, some 77 mutated proteases have been identified to date which often contribute to hereditary diseases and, therefore, represent target opportunities.

Figure 7.1 

Protease Inhibitors: Innovation Drives Drug Pipeline seeks to provide a comprehensive assessment of those protease inhibitors that have been reported as in active development in late 2008, and to highlight the areas on which pharmaceutical and biotechnology companies are currently focusing their research efforts. To clearly understand the complexities of protease inhibitor development, this report reviews the various classes of proteases following the systematic classifications that have evolved, while considering some of the technical problems that have complicated protease inhibitor development.

Protease Inhibitors: Innovation Drives Drug Pipeline highlights the commercial successes that have been achieved to date, primarily with respect to ACE inhibitors and HIV protease inhibitors. The report then considers development pipelines by therapeutic area rather than by specific classes of protease targets due to the diversity of potential therapeutic indications in which protease inhibitors are of potential value. The report also includes brief profiles of the protease inhibitor activity within major pharmaceutical companies and selected biotechnology companies.

Protease Inhibitors: Innovation Drives Drug Pipeline looks at some 20 protease inhibitors, and three fixed-dose combinations in advanced development that are expected to be submitted for FDA approval in the period between late 2008 and 2013. This analysis clearly indicates that the successful development of protease inhibitors offers significant therapeutic and commercial benefits. Several of these protease inhibitors are expected to achieve major commercial success.  The report also focuses on a considerable number of protease inhibitors that are in development and may reach NDA submission status by the end of this period. 
About the Author
Peter Norman, PhD, MBA, is a pharmaceutical consultant and analyst based in Burnham Beeches, near Windsor, England. He has written and presented widely on various aspects of respiratory disease, drug development, and the analysis of diverse therapeutic markets. Dr. Norman has more than 20 years of experience in the pharmaceutical industry in both R&D and competitive intelligence. His publications include many reviews, 16 original scientific papers, and 11 patents, together with a number of industry reports, including the Insight Pharma Report, Kinase Therapeutic Pipelines: An Assessment of Targets and Agents in Development (http://www.insightpharmareports.com/reports/2007/90_Kinase_Inhibitors/overview.asp). Dr. Norman holds science degrees from Cambridge University and Brunel University and an MBA degree from the Open University.