<i>In vitro</i> and <i>in vivo</i> ADME of heterobifunctional degraders: a tailored approach to optimize DMPK properties of PROTACs©
Christine K. Maurer, Zhizhou Fang, Christina Schindler, Gianna Pohl, Fouzia Machrouhi‐Porcher, Marc Lecomte, Carl Petersson, Heide Marika Duevel
Abstract
This study suggests a tailored in vitro DMPK discovery assay cascade and frontloading in vivo studies. It also underlines the need for inclusion of surrogate permeability descriptors and experimentally determined values for IVIVE of CL int .
Topics & Concepts
ADMEIn vivoIn vitroComputational biologyDrug discoveryCascadeChemistryIn vitro toxicologyPharmacologyBiochemical engineeringBiologyBiochemistryChromatographyEngineeringBiotechnologyProtein Degradation and InhibitorsReceptor Mechanisms and SignalingPeptidase Inhibition and Analysis