Klara Valko | Authors


Biomimetic Chromatography to Accelerate Drug Discovery: Part 2

The biomimetic gradient retention time measurements on C18, immobilized artificial membrane (IAM), human serum albumin (HSA), and acid-glycoprotein (AGP) stationary phases can be used to characterize compounds partitioning into phospholipids and proteins. The data obtained can then be used in equations to estimate the in vivo plasmaÐtissue distribution of the compounds measured. The plasma protein binding, brain tissue binding, and in vivo drug efficiency can also be calculated using the biomimetic chromatographic data.

Biomimetic Chromatography to Accelerate Drug Discovery: Part 1

The drug discovery process can be accelerated by chromatographic profiling of analogs by measuring their nonspecific binding to proteins and lipids and then by modelling in vivo distribution. A balanced potency and chromatographically determined membrane and protein binding ensure the selection of compounds with the highest probability to show the desired in vivo distribution behaviour for efficacy and reduced toxicity. The first part of the article will discuss the high performance liquid chromatography (HPLC)-based measurements of lipophilicity and biomimetic properties, while the second part will discuss the models derived from the measured data of known drug molecules and drug discovery compounds.