Label-free technology and patient cells: from early drug development to precision medicine.

Drug development requires physiologically more appropriate model systems and assays to increase understanding of drug action and pathological processes in individual humans. Specifically, patient-derived cells offer great opportunities as representative cellular model systems. Moreover, with novel label-free cellular assays, it is often possible to investigate complex biological processes in their native environment.

Phenotypic screening of cannabinoid receptor 2 ligands shows different sensitivity to genotype.

The Cannabinoid Receptor 2 (CBR) is a G protein-coupled receptor (GPCR) investigated intensively as therapeutic target, however no drug has reached the market yet. We investigated personal differences in CBR drug responses using a label-free whole-cell assay (xCELLigence) combined with cell lines (Lymphoblastoid Cell Lines) from individuals with varying CBR genotypes. Responses to agonists, partial agonists and antagonists of various chemical classes were characterized.

Whole-cell biosensor for label-free detection of GPCR-mediated drug responses in personal cell lines.

Deciphering how genetic variation in drug targets such as G protein-coupled receptors (GPCRs) affects drug response is essential for precision medicine. GPCR signaling is traditionally investigated in artificial cell lines which do not provide sufficient physiological context. Patient-derived cell lines such as lymphoblastoid cell lines (LCLs) could represent the ideal cellular model system.

Drug-target residence time--a case for G protein-coupled receptors.

A vast number of marketed drugs act on G protein-coupled receptors (GPCRs), the most successful category of drug targets to date. These drugs usually possess high target affinity and selectivity, and such combined features have been the driving force in the early phases of drug discovery. However, attrition has also been high.