Computational prediction of Calu-3-based in vitro pulmonary permeability of chemicals

Pulmonary is a potential route for drug delivery and exposure to toxic chemicals. The human bronchial epithelial cell line Calu-3 is generally considered to be a useful in vitro model of pulmonary permeability by calculating the apparent permeability coefficient (Papp) values. Since in vitro experiments are time-consuming and labor-intensive, computational models for pulmonary permeability are desirable for accelerating drug design and toxic chemical assessment. This study presents the first attempt for developing quantitative structure-activity relationship (QSAR) models for addressing this goal. A total of 57 chemicals with Papp values based on Calu-3 experiments was first curated from literature for model development and testing. Subsequently, eleven de-scriptors were identified by a sequential forward feature selection algorithm to maximize the cross-validation performance of a voting regression model integrating linear regression and nonlinear random forest algo-rithms. With applicability domain adjustment, the developed model achieved high performance with correlation coefficient values of 0.935 and 0.824 for cross-validation and independent test, respectively. The preliminary results showed that computational models could be helpful for predicting Calu-3-based in vitro pulmonary permeability of chemicals. Future works include the collection of more data for further validating and improving the model.

Automated summary

This study presents the development of a computational model for predicting in vitro pulmonary permeability of chemicals. By integrating multiple algorithms and applying applicability domain adjustment, the model achieved good performance in both cross-validation and independent testing.