IN VIVO METHODS OF DETERMINING ACTIVITY OF RECEPTOR-TYPE KINASE INHIBITORS

摘要

In vivo methods are disclosed for measuring compound inhibition of kinase receptor activity. Examples are provided which show a direct correlation between in vivo inhibition of KDR kinase inhibition and circulating blood and plasma levels of the inhibitor. These data are used to predict and validate non-quantifiable in vitro measurements, such as murine endothelial cell IC50 values. The in vivo potency of a compound determined by an assay of the present invention may be utilized to select dose amounts and frequencies for further preclinical animal model studies and human clinical studies designed to generate safety, potency and efficacy profiles for the respective inhibitor.