Kinase Research

Protein Kinases and Disease

Protein kinases are responsible for the normal regulation of numerous cellular functions including cell proliferation and differentiation. Unregulated activation of kinases through point mutations and/or overexpression can result in the development of diseases, including cancer and inflammatory diseases.

Many of the genes already known to be involved in the development of cancer are protein kinases and recent research is revealing that different combinations of protein kinases may be critical in the development and progression of various cancers. In tumor cells, protein kinases provide tumor-specific targets for drugs that may work as stand-alone therapies or enhance traditional chemotherapy/radiation therapy with minimal added side effects.

Proven Therapeutic Success... and Challenges

Drug development of kinase inhibitors for cancer has been validated by the success of FDA-approved small molecule and antibody therapies, including Herceptin® (Genentech/Roche), Gleevec® (Novartis), IRESSA® (AstraZeneca), ERBITUX™ (ImClone/Bristol-Myers Squibb), Tarceva® (Genentech/Roche/OSI), Sutent® (Pfizer) and Nexavar® (Onyx/Bayer). With more than 500 distinct protein kinases identified through the human genome project and over 30 kinase inhibitors in clinical trials or approved for human use, this important class of proteins is a rich area for therapeutic drug development.

While kinase inhibitors hold great promise in many diseases, target selectivity is a serious and common problem in drug development. Inhibition of a single off-target kinase could induce toxicity and undermine an entire clinical program. And, as the development of targeted kinase inhibitors advances, the questions of how to design a multi-targeted kinase inhibitor without widespread toxicity is increasingly an issue.

Historically, drug development scientists used a "check the box" approach to inspect the specificity of a given compound. Using a traditional enzyme assay and a subjective ATP concentration, scientists were afforded a limited glimpse of the potential effects of their compound on the large kinase family of enzymes. KINOMEscan™ is overturning this mindset by fully characterizing libraries and generating a broad understanding of the collection. Promising leads are determined from medicinal chemistry feedback and are further developed and quickly re-profiled to demonstrate an improved selectivity. Even existing clinical compounds can be evaluated to reveal new indications. KINOMEscan™ is an integrated partner throughout the drug discovery and development process.

KINOMEscan™ is a key partner throughout drug discovery and development. KINOMEscan™ is utilized by scientists through the entire discovery and clinical development continuum. Compound libraries are characterized not only for specificity and optimization, but also for novel indications and clinical opportunities.

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