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Kinase-Targeted Therapeutics: Development Pipelines, Challenges, and Opportunities

0 Pages CHI Insight Pharma Reports August 01, 2011 SKU: CHI6709556

The field of kinase modulation is one of the most active in the biopharmaceutical industry. About 20 kinase inhibitors are approved for marketing in the United States and at least another 250 are in clinical evaluation. Kinases make up a veritable treasure trove of targets for a variety of indications. This report analyzes:

  • The considerable array of therapeutic development efforts directed at kinases
  • Current and emerging technologies being applied to development of these compounds
  • The major companies and projects involved with kinase modulation
  • How unique characteristics of different kinase classes impact therapeutic development
  • Current trends and major challenges faced by the industry
The role of kinases in cellular function and communication, coupled with their sheer number, suggests that any disruption in their activity can have adverse effects. Aberrant or inappropriate kinase activity has been associated with many diseases, in particular those involving inflammatory or proliferative responses. In addition to cancer and inflammatory disorders such as rheumatoid arthritis, compromised kinase activity has been causally linked to diabetes, cardiovascular disease, neurological disorders, and other conditions. The most advanced compounds in clinical development target only a handful of the best-characterized kinases. Beyond these kinase targets, hundreds more exist that could provide sites for intervention in other disease processes.

Most, if not all, big pharma firms have programs in the area of kinase modulation, and they are included among the leaders in the field. Small-molecule kinase inhibitors are the most promising types of drugs in this class because of their potential for oral delivery, the ease of fine-tuning their chemical structure using classic and combinatorial chemistry techniques, and their amenability to large-scale production. Monoclonal antibodies, antisense, and RNA interference are also being targeted against kinases. Kinase-Targeted Therapeutics: Development Pipelines, Challenges, and Opportunities considers both small-molecule and biologic kinase-targeted agents in development. We review the current R&D pipeline of products, organized according to the major groups: the receptor and nonreceptor tyrosine kinases; and the serine-threonine kinases.

A large proportion of late-stage clinical kinase inhibitor programs target receptor tyrosine kinases. Although only 58 of the 518 human kinases fall into this category, their role in controlling cellular growth and the fact that they possess extracellular binding domains made them early and actively explored targets for the development of compounds for cancer and other proliferative diseases. Almost 40% of kinase inhibitors in clinical trials fall into this category. Companies are, however, working to design improved agents that target a wide range of combinations of these kinases. The role of the PI3K-Akt-mTOR pathway in cancer is now also generating increased interest, as many pharmaceutical companies are in the early stages of building programs in this area.

While kinase modulation has shown itself to be a novel and promising approach to treating disease, several limitations have become apparent in studies that have been conducted to date. Kinase-Targeted Therapeutics: Development Pipelines, Challenges, and Opportunities explores some of the challenges to success in the field, including:

  • Ensuring target relevance and specificity
  • Overcoming resistance
  • Designing clinical trials to maximize the response to a drug
  • Addressing the high cost of novel therapeutics

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Kinase-Targeted Therapeutics: Development Pipelines, Challenges, and Opport...

CHI Insight Pharma Reports
August 01, 2011

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