A priori inference of cross reactivity for drug-targeted kinases.

摘要: Kinases are central targets for drug-based treatment of diseases such as cancer, diabetes, and arthritis. Progress in drug development faces challenges due to undesirable cross reactivity difficulties modulating selectivity, both consequences fold conservation. Here we present a structure-based predictor validate it against affinity fingerprinting the kinases our own redesign geared at sharpening inhibitory impact. The assesses protein environments binding pockets, compares patterns packing defects, introduces distance kinase space. This metric is conclusively shown be equivalent pharmacological generated by comparing fingerprintings. Our further extended infer over all human tyrosine kinases. tool should prove useful target clinically relevant regions pharmacokinome, experimental assays reveal.