Kinases: Advanced Strategies and Multiple Targets for Drug Discovery

Abstract

The kinase-targeted drug market is forecast to reach $58.6 billion in 2010.

D&MD's Kinases: Advanced Strategies for Drug Discovery market analysis report comprehensively reviews protein kinases and assesses their importance as drug targets. Approaches to kinase drug discovery are evolving. Small molecule inhibitors now encompass rationally-designed single-target inhibitors and multi-target inhibitors developed with the aid of new screening and profiling assays. Innovative biopharmaceuticals are making inroads into the market. The range of indications for kinase-targeted drugs is expanding.

During the last five years, eight anticancer kinase inhibitors received FDA approval, including multi-kinase inhibitors, the first of which was approved by the FDA in December 2005. The launched drugs are discussed in this report, as are similar agents that are following in their track. At the same time, recent discoveries of activating and resistance kinase mutations have been driving the development of molecularly targeted anticancer therapies and we review progress in this area. An on-line survey conducted specially for this report shows that kinases (alongside GPCRs), are currently regarded as commercially the most promising targets available to the drug industry. The facts and analysis provided by this report help companies prepare themselves to exploit these targets.

Chapter 1: E xecutive Summary

During the last five years, eight anticancer kinase inhibitors received FDA approval, increasing recognition of kinases as an important class of drug targets. In order to comprehensively assess the scientific, clinical, and commercial progress and prospects in this field, the following surveys were carried out exclusively for this report: a search of Pharmaprojects, the leading database tracking pharmaceutical R&D worldwide; a survey of the last six years of kinase-related patenting at the US PTO; and an on-line survey of pharmaceutical industry and academic personnel. We forecast that the kinase-targeted drug market will grow from $12.7 billion in 2005 to $58.6 billion in 2010. Cancer (mainly solid tumors) will remain the dominant application throughout the forecast period.

Reversible protein phosphorylation, catalyzed by kinases, is a ubiquitous mechanism for the control of signal transduction networks that regulate many vital biological processes. Cancer and other proliferation-related disorders are associated with stimulation of intra-cellular signaling, and since kinases (most of the time) positively relay signaling events; their inhibition offers a powerful way to block aberrant signal transduction cascades. The focus throughout this report is on inhibitors of protein kinases, although, where appropriate, protein kinase stimulators are also discussed, as are modulators of lipid and sugar kinases. The search of the Pharmaprojects database generated 803 drug profiles representing 243 unique companies, 184 unique targets, and 68 unique indications/drug types. A subsequent search of the Entrez Gene database for human genes with kinase activity led us to conclude that (according to Pharmaprojects) 145 kinase-related genes are currently drug targets, while 627 kinase-related genes remain unexplored as drug targets.

Examination of the Pharmaprojects dataset revealed that the kinase drug market is at an early stage; overall 80% of drugs are still in preclinical development. By far the largest indication for kinase-targeted drugs, almost 41% of the total, is cancer. Of the top five kinase drug targets, only one is not primarily a cancer target. Other important indications for kinase-targeted drugs include inflammation, arthritis, diabetes, and cardiovascular disease. Of the top ten companies most active in this area, only Pfizer, Novartis, AstraZeneca, and GlaxoSmithKline have launched products.

Currently, the emphasis is on small molecule approaches to kinase inhibition. The majority of the respondents to our on-line survey felt that small molecule inhibitors were preferable to monoclonal antibodies and that multi-target kinase inhibitors were more likely to prove commercially successful than single-target inhibitors. Now that many kinases have been sequenced and their structures have been determined, more efficient approaches to small molecule kinase inhibitor discovery are urgently needed. We discuss recent advances in this area,

Buy this report and receive:

• Results from a survey of more than 800 kinase drugs and their targets to give the reader an appreciation of the kinase drug landscape
• Current market size and forecasts to 2010 to assist the reader with formulating business plans in the kinase drug area
• Analysis on the leading indications for kinase drugs and highlights in areas of unmet needs to enable the reader to formulate a strategy for business development
• Profiles of kinase-related patenting at the US PTO to help the reader understand the area's evolving IP landscape, identify trends, improve strategic approach and discover potential collaborative partners
• Comprehensive analysis of kinase drug targets through a gene family-based approach to allow the reader to assess the drug development potential of kinases belonging to particular families

Receive answers to crucial questions in this area such as:

• Which kinase targets are being pursued by drug developers?
• Which kinase targets have attracted the greatest amount of interest from drug developers?
• What is the nature of commercial activity surrounding each major kinase target?
• Which are the most important therapeutic indications for kinase drugs?
• What are the areas of unmet need that new kinase drugs could address?
• Which companies are the most prolific developers of kinase drugs and what drugs are in their portfolios?
• Who are the most prolific assignees and which are the most frequently cited kinase patents?

Recent approvals of several first-in-class kinase inhibitors have resulted in increased recognition of kinases as an important class of drug targets. The kinase market is still at an early stage, but many trends are already evident and these are analyzed in this report. Already 145 kinase-related genes are being targeted in kinase drug development, which nonetheless leaves a large number (estimated 627) of potential targets unexplored. This report guides readers in assessing or reassesing their strategies with respect to this target class.

In order to comprehensively assess recent progress and prospects in the kinase field, several surveys were carried out exclusively for this report, involving searches of the Pharmaprojects database and the U.S. Patent and Trademark Office database, and questioning of respondents from the pharmaceutical industry. The information from the various surveys was utilized in the analysis of individual kinase targets and families to which they belong.