Recent developments in the application of immobilized artificial membrane (IAM) chromatography to drug discovery

Immobilized artificial membrane (IAM) chromatography is widely used in many aspects of drug discovery. It employs stationary phases, which contain phospholipids combining simulation of biological membranes with rapid measurements.

Advances in IAM stationary phases, chromatographic conditions and the underlying retention mechanism are discussed. The potential of IAM chromatography to model permeability and drug-membrane interactions as well as its use to estimate pharmacokinetic properties and toxicity endpoints including ecotoxicity, is outlined. Efforts to construct models for prediction IAM retention factors are presented.

IAM chromatography, as a border case between partitioning and binding, has broadened its application from permeability studies to encompass processes involving tissue binding. Most IAM-based permeability models are hybrid models incorporating additional molecular descriptors, while for the estimation of pharmacokinetic properties and binding to off targets, IAM retention is combined with other biomimetic properties. However, for its integration into routine drug discovery protocols, reliable IAM prediction models implemented in relevant software should be developed, to enable its use in virtual screening and the design of new molecules. Conversely, preparation of new IAM columns with different phospholipids or mixed monomers offers enhanced flexibility and the potential to tailor the conditions according to the target property.