Permeability and Transporter Study

WuXi AppTec DMPK's in vitro permeability and transporter platform pays great attention to in vitro to in vivo correlations (IVIVCs) of in vitro models. For example, the IVIVC validation of Caco-2 permeability model was carried out using model drugs to define the binning criteria in 2015. Since then, the experiment has been repeated annually, and the results are reproducible. As shown in Figure 1, in the experiment conducted in 2024, the P_app (A-B) values of 25 commercially available drugs correlated very well with the human absorption data ² (R² of 0.9205).

Brain penetration is one of the key factors for CNS drug development. WuXi AppTec DMPK's in vitro permeability and transporter platform developed a “Screening Funnel” model for brain penetration assessment. Ten “CNS+” drugs (high brain penetration, triangles) and 14 “CNS-” drugs (low brain penetration, dots) were included in the validation (Figure 2). All these drugs were tested in BBB-PAMPA, and ten “CNS-” drugs (red dots) were excluded due to limited BBB penetration. The others were tested in the MDR1-MDCK I (NIH) assay, and four “CNS-” drugs (blue dots) were further excluded due to high P-gp efflux. The remaining 10 compounds were potential “CNS+” (high brain penetration) compounds and were classified correctly.