Introduction: Lipophilicity, expressed as the octanol-water partition coefficient, constitutes the most important property in drug action, influencing both pharmacokinetic and pharmacodynamics processes as well as drug toxicity. On the other hand, biomimetic properties defined as the retention outcome on HPLC columns containing a biological relevant agent, provide a considerable advance for rapid experimental – based estimation of ADME properties in early drug discovery stages. Areas covered: This review highlights the paramount importance of lipophilicity in almost all aspects of drug action and safety. It outlines problems brought about by high lipophilicity and provides an overview of the drug-like metrics which incorporate lower limits or ranges of logP. The fundamental factors governing lipophilicity are compared to those involved in phospholipophilicity, assessed by Immobilized Artificial Membrane Chromatography (IAM). Finally, the contribution of biomimetic properties to assess plasma protein binding is evaluated. Expert opinion: Lipophilicity and biomimetic properties have important distinct and overlapping roles in supporting the drug discovery process. Lipophilicity is unique in early drug design for library screening and for the identification of the most promising compounds to start with, while biomimetic properties are useful for the experimentally-based evaluation of ADME properties for the synthesized novel compounds, supporting the prioritization of drug candidates and guiding further synthesis.

Introduction: The development of immobilized artificial membrane (IAM) chromatography has unfolded new perspectives for the use of chromatographic techniques in drug discovery, combining simulation...

Bauxite residue (BR) is a well promising resource for critical metals, especially scandium (Sc), a rare and expensive metal with increasing applications in advanced technology. Greek BR seems to significantly favor a commercially viable recovery of Sc combining optimized leaching and advanced separation techniques. Leaching with mineral acids emerges as the dominant selection compared to other techniques. This study investigates an optimized leaching condition set for Sc recovery, using the most advantageous option of sulfuric acid. The main target is to develop a leaching scale-up process to be established in the premises of Mytilineos S.A. (formerly Aluminium of Greece, the largest Greek alumina and aluminum producer), taking into account the feed requirements of a subsequent advanced ion exchanged procedure. Several parameters were studied individually or combined in order to achieve high Sc concentration in the leachate and to ensure selectivity, especially concerning iron. The most significant parameters prove to be the solid-to-liquid ratio (S/L), the final pH value, and the leachate’s recycling. The proposed process, with low molarities of sulfuric acid and ambient conditions, integrates rapidly, leading to high and selective Sc recovery. Finally, a leaching process flow diagram under continuous operation on an industrial scale is developed.

The major causes of failure of drug discovery compounds in clinics are the lack of efficacy and toxicity. To reduce late-stage failures in the drug discovery process, it is essential to estimate early the probability of adverse effects and potential toxicity. Cardiotoxicity is one of the most often observed problems related to a compound's inhibition of the hERG channel responsible for the potassium cation flux. Biomimetic HPLC methods can be used for the early screening of a compound's lipophilicity, protein binding and phospholipid partition. Based on the published hERG pIC50 data of 90 marketed drugs and their measured biomimetic properties, a model has been developed to predict the hERG inhibition using the measured binding of compounds to alpha-1-acid-glycoprotein (AGP) and immobilised artificial membrane (IAM). A representative test set of 16 compounds was carefully selected. The training set, involving the remaining compounds, served to establish the linear model. The mechanistic model supports the hypothesis that compounds have to traverse the cell membrane and bind to the hERG ion channel to cause the inhibition. The AGP and the hERG ion channel show structural similarity, as both bind positively charged compounds with strong shape selectivity. In contrast, a good IAM partition is a prerequisite for cell membrane traversal. For reasons of comparison, a corresponding model was derived by replacing the measured biomimetic properties with calculated physicochemical properties. The model established with the measured biomimetic binding properties proved to be superior and can explain over 70% of the variance of the hERG pIC50 values. ©2021 by the authors. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).