Attentive graph neural network models for the prediction of blood brain barrier permeability.

The blood brain barrier's (BBB) unique endothelial cells and tight junctions selectively regulate passage of molecules to the central nervous system (CNS) to prevent pathogen entry and maintain neural homeostasis. Various neurological conditions and neurodegenerative diseases benefit from small molecules capable of BBB penetration (BBBP) to elicit a therapeutic effect. Predicting BBBP often involves assessment of molecular properties such as lipophilicity (log ) and polar surface area (PSA) using the CNS multiparameter optimization (MPO) method.

AlphaLogD determination: An optimized Reversed-Phase Liquid Chromatography method to measure lipophilicity on neutral and basic small and Beyond-Rule-of-Five compounds.

Lipophilicity can be measured with different methods, such as Shake-Flask or liquid chromatography. HPLC presents the advantage of overcoming solubility issues and therefore extending the range of lipophilicity to high values. A specific HPLC method, called ELogD, had been developed 20 years ago on a C-amide stationary phase, enhancing hydrophobic and hydrogen bond interactions to mimic octanol-water partition.