Scientific Programmes

Experimental Therapeutics Programme

Biology Section

Head of Section:  Carmen Blanco

In the Experimental Therapeutics Programme, we are working on both targeted and phenotypic-based drug discovery projects. In the targeted projects, the Biology Section is devoted to the biochemical, cellular, and in vitro/in vivo pharmacological characterisation of the compounds synthesised within the Programme. Our aim is to obtain novel anticancer agents with optimised profiles that are able to demonstrate in vivo proof of concept in animal models of cancer.

In phenotypic-based projects, we perform target engagement and target deconvolution tasks using label-free techniques and chemical probes, respectively. The cellular thermal shift assay is a label-free technology that enables drug binding studies to target proteins in their relevant cellular contexts. Alternatively, we use engineered chemical probes to deconvolute the possible targets of our molecules. For that purpose, we first have to confirm that they behave similarly to the parent compound in the phenotypic screening.

These molecules bear a linker with functionalities that permit their crosslinking with targeted proteins and the attachment of reporter tags for imaging and pull down experiments in cells and cell lysates. Thus, through immunofluorescence assays, we can determine the cellular localisation of the complex of the chemical probe with its targets and, by pull down experiments, using active and inactive chemical probes also in competition with the parent compound followed by mass spectrometry analysis, we can identify candidate targets for the observed phenotype.

Furthermore, in exploratory screening projects carried out in collaboration with other CNIO Groups, we provide support by preparing customised compound assay plates from our ETP-libraries, adding the compounds using automated liquid-handling instruments that allow rapid, accurate, and reproducible compound dispensing and assay plate setup. All this instrumentation is integrated in a platform that allows sample tracking and recording.