Drug metabolism includes a wide range of biochemical processes, which finally lead to either drug inactivation or drug transformation, which facilitates the elimination of xenobiotics from the human body.

Drugs can be metabolized in different organs, such as intestines, kidneys, spleen, lungs, however, for the large majority of pharmaceutical drug metabolism occurs in the liver.
Therefore, assessment of in vitro intrinsic clearance or identification of metabolites formed is crucial at an early stage of the drug discovery process.

In vitro…

Human induced pluripotent stem cells (hiPSC) are obtained by genetically reprogramming somatic cells from human tissues, after which these cells can be further differentiated virtually into any cell types. hiPSC are derived from normal adults or from diseased patients and carry protein mutations that are able to compromise the cell physiology.

As consequence, hiPSC-derived cells reveal a high potential for studying pathophysiological processes in basically all pathological areas including CNS, PNS, peripheral tissues (cardiac, hepatic, pulmonary, muscular, vessel, blood, etc.)…

What

Flow chemistry is a technology for organic synthesis where, using an apparatus of microfluidics, reactants are brought together within small reaction volumes and reaction products are collected as part of an ongoing flow process.  In such a flow process the reaction is initiated and continues with a constant fresh supply of reactants until such time when reagents are exhausted or the reaction is stopped by the chemist or operator. 

Why

Flow chemistry offers an interesting…

The generation of cell lines overexpressing particular proteins on which drug discovery programs are often based, is necessary for assay development in screening campaigns using initial target-based identification of hit compounds. Recombinant stable cell lines are also used for toxicity studies and general in vitro testing.

Methods to be used and the cell background for the generation of a cell line could depend on several factors: i) the complexity of protein (e.g. dimensions, carrying antibiotic resistance, presence of tags etc.)…

Proteins typically undergo a proper folding via intracellular chaperone machinery. Folding confers to proteins the spatial characteristics that define their role in the cells, however the folding process might not always work properly. For intrinsic changes of protein characteristics (e.g. mutations and/or improper elongation, PTMs etc.) or for defective chaperone activity, proteins can assume a wrong conformation. In this case complex intracellular degradative systems are able to recognize the misfolded proteins and provide their degradation and clearance, through the ubiquitin-proteasome…