BACKGROUND

 

Rapid, Quantitative Profiling and Drug Selectivity Screening of Native Protein Kinases

ActivX has pioneered the commercialization of Activity-Based Protein Profiling (ABPP). Starting with serine hydrolases, ActivX has developed novel platforms and probes to broadly and accurately profile pharmaceutically-relevant protein activities directly in biological samples.

KiNativ™ brings the power of ABPP to the functional analysis of native protein kinases. Rapid, quantitative profiling and drug selectivity screening of protein kinases is now possible directly in virtually any biologic sample. Protein kinases represent the largest single group of mammalian enzymes and have generated intense focus for pharmaceutical development. The fulfillment of the promise of protein kinase-directed therapeutics has been hindered both by the lack of drug selectivity amongst the roughly 500 known human protein kinases and the tremendous complexity of protein kinase activity regulation in vivo. KiNativ™ addresses both of these key issues by providing a single platform to comprehensively assay protein kinases (as well as other ATP-binding proteins) directly in relevant biological samples where native post-translational modifications and protein-protein interactions are preserved.

Drug selectivity is a principle concern for the development of protein kinase-based therapeutics. Currently the most comprehensive kinase screens only cover approximately 50% of the predicted protein kinases. The KiNativ™ platform significantly expands overall protein kinase coverage and can be used to profile over 400 known human protein kinases (shown below in red). The KiNativ™ Platform has identified more than 400 of the 500 protein kinases (shown above in red).

 

In Situ Lipid Kinase Profiling

ActivX is pleased to announce the expansion of our KiNativ™Platform with the introduction of a comprehensive lipid kinase and lipid kinase related protein kinase panel. Several lipid kinases, particularly members of the phosphatidyl-inositol 3-kinase (PI3K) family, have emerged as attractive drug targets for inflammation and cancer. These enzymes have been notoriously difficult to assay given their large molecular weight (>100 kDa) and the difficulty in expressing them recombinantly. Additionally, nearly all of the clinically attractive lipid kinase targets are known to exist as multi-protein complexes that regulate their substrates and activation states. Our new Lipid Kinase Profiling Panel contains the highly studied PI3K protein family along with many of the other known lipid and inositol kinases. This panel has been validated for profiling native PI3/4 kinases, PI3K related protein kinases, PIP4/5 kinases, diacylglycerol kinases, ITPKs and more. The profiling is performed directly in cell lysates, utilizing full length proteins, that still maintain their complex protein-protein interaction.

Please refer to our lipid kinase brochure for more details.