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Profiling the kinetic selectivity of kinase marketed drugs

 Jun, 12-13th 2017

Enzymlogic announce the presentation of results achieved with its Binding Kinetic Platform in the evaluation of the kinetic profile of kinase-marketed drugs.


Enzymlogic announce the presentation of results achieved with its Binding Kinetic Platform in the evaluation of the kinetic profile of kinase-marketed drugs. The poster entitled “Profiling the kinetic selectivity of kinase marketed drugs” will be presented at 18th Drug Discovery Summit in Berlin, June 12th to 13th, 2017. This study provides a deeper understanding of how the early evaluation of kinetic selectivity can help to improve decision-making, leading to a better selection of interesting compounds to be further profiled.

Enzymlogic Foretinib kinase kinetic selectivity

The Human Protein Kinases

Protein kinases represent one of the largest protein families, with more than 500 encoded in the human genome. Their importance is further reflected in the fact that phosphorylation is the most abundant type of cellular regulation, affecting essentially every cellular process, including metabolism, growth, differentiation, motility or membrane transport. For these reason, kinases have been established as promising drug targets for the treatment of various types of human disease.


Beyond potency measurements: what is the value of Kinetic Selectivity in drug discovery?

One of the main challenges in drug discovery is the design of inhibitors with an appropriate balance between drug efficacy and potential adverse effects as early as possible in order to reduce the likelihood of safety issues. The characterization of compound selectivity has been traditionally focused on potency, where concentration-dependent parameters are measured at equilibrium. There is, however, a growing evidence for the physiological relevance of the temporal aspects of kinase-inhibitor interactions and the need of applying binding kinetics to optimize the temporal and functional response profiles of future drug candidates. In the study, the kinetic selectivity profiling of several marketed drugs reveals that parallel affinity and kinetic profiling of a compound towards multiple kinases is a power tool to design inhibitors with the desired selectivity profiles. We have found that compounds with identical affinity for a given kinase can exhibit very different kinetic profiles, which may be the reason for their tolerability in patients.


About Enzymlogic

Enzymlogic offers in vitro biochemical and cell-based assays to the biotechnological and pharmaceutical companies, life science laboratories and academic groups. Our binding kinetics, kinetic selectivity, assay development, profiling and screening services enable faster and cost-effective drug discovery by identifying the most promising drug candidates as well as withdrawing those compounds likely to fail in pre-clinical development. Additionally, Enzymlogic’s pioneering approach provides predictive tools that deliver physiologically relevant insights earlier in the drug discovery process.

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