The aProximateTM Proximal Tubule Cell (PTC) model offers a cutting-edge platform for the evaluation of drug-induced nephrotoxicity, radioconjugate retention and the accumulation of large molecules (ADCs, ASO, antibiotics, peptides, etc) in the proximal tubule. This white paper outlines the advantages of using the aProximateTM PTC model in predicting and assessing renal safety in the early stages of drug development, focusing on its application in the context of renal radioconjugates and large molecule dynamics.

Model Overview
The aProximateTM PTC model replicates the physiology and function of human proximal tubule cells. These cells are crucial for assessing kidney toxicity, drug-drug interactions and the pharmacokinetics of new therapeutics, not only of traditional small molecules, but also of the new modalities of large molecules and particularly radioconjugates, which are prone to renal accumulation. The cells in the model maintain differentiation, expressing high levels of renal transporter, including Megalin and Cubilin, which mediate protein and
large molecule uptake in the nephron (Figure 1.). This model has been validated against various parameters, including Trans Epithelial Electrical Resistance (TEER), uptake and flux of small and large molecules and specific biomarker expression of toxicity, ensuring its physiological relevance and accuracy in safety evaluations.