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Experimental ADMET parametersAbsorption, distribution, metabolism and excretion charcteristics of the compounds and the nature and kinetics of the metabolites and toxicology testing is carried out early in the drug developmental process. The physicochemical properties of a compound have high influence on its pharmacokinetic profile. ATP-competitive kinase inhibitors do have common properties, which result in some subsequent ADMET issues. In order to optimally bind to the hydrophobic backpocket, they need to be lipophilic. As adenine mimicks, they have a planar structure, in addition to the poor solubility. Due to the intracellular nature of kinases, inhibitors must be highly permeable, which is an issue since the chemical structure of hinge binders bears permeability problems. Finally, these compounds compete with ATP, which means that high levels of compound and/or a high level selectivity for one particular target are needed. Having mentioned the intrinsic ADMET issues of kinase inhibitors, we typically try to calculate those properties upfront by using computer-aided ADMET technologies and we also established an in vitro ADMET platform. We measure the following Experimental ADMET parameters:
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