Drug discovery platform

At IRB Barcelona, we have set up a screening platform with state-of-the-art technology, which allows HTS and provides support for Hit to Lead and Lead Optimisation projects in an efficient and automated way. Different assays/process can be run in parallel in an integrated or stand-alone manner. The platform is equipped with the following: Cell Explorer workstation from Perkin Elmer: robotic arm platform with up-to-date software and high storage capacity for processing assay plates in an automated way, allowing integration with all the robots used by the platform. Envision plate reader from Perkin Elmer: compatible with several technologies (Fluorescence, Ultraluminescence, Absorbance, FRET, Alpha and Fluorescence Polarisation). Echo 650 from Beckman Labcyte: acoustic dispenser able to add nano-drops of 2.5 nl, measure DMSO content and avoid cross-contamination (tip-free system); compatible with viscous samples such as natural extracts. Multidrop dispenser from Thermo: bulk dispenser able to add volumes from 1,000 μl to as little as 1 µl. Zephyr from Perkin Elmer: 96-well pipettor BIOTEK washer: 96 and 384 plate washer. Automated plate incubator for biochemical or cell-based experiments with temperature, CO2 and humidity control. Compound Library 50,000 compounds from the ChemDiv library, representative of more than 1,500,000 compounds. Moreover, the library contains focused subsets such as Protein-Protein-Interaction (PPI), CNS, cancer, diverse set and lead-like set, among others. 2,400 compounds from the FDA-approved drug collection from MCE. Constantly growing with the goal to reach more than 100,000 compounds (including proprietary and novel ones) by 2024.

We offer full drug discovery support tailored to researchers’ needs, from experimental design to wet-lab validation, with the possibility of chemo- and bioinformatics analysis. We assess theoretical feasibility in terms of the relevance of the assays, throughput level and technical feasibility. This is followed by assay development, accomplishing industrial standards. The instrumentation available in the DSP is compatible with libraries of small molecules, biological extracts, peptides, antibodies and other molecules. Our services include: Experimental design and feasibility: Project assessment regarding the relevance of biological assays, technologies, cost-effectiveness and screening cascades not only in terms of efficacy but also DMPK (Drug Metabolism and Pharmacokinetics) and safety. Assay development: Following industrials standards, we ensure the best conditions for your assays in the presence and absence of standard compounds (kinetics, assay component titrations, assay miniaturisation, compound pre-incubation, etc.) and DMSO effect, reproducibility, signal and reagent stability and Z´ factors, among others. HTS: Screening of the set of compounds/extracts (from small to large sets comprising 200,000 compounds or more). The process involves a pilot screen (about 2,000-5,000 compounds), screening of the library (from small sets to more than 200,000 compounds), and confirmation and hit validation using orthogonal and dose-response assays. Moreover, we can perform chemical clustering. Synergism: Assessing the effect of interactions between the different components. Hit-to-Lead and Lead Optimisation: Testing of several compounds in dose-response mode (more than 64 compounds at 10 doses, in duplicates, per day) and characterisation of the mechanism of action (binding mechanism, residence time etc) among others. We can work with biochemical and cellular assays in both 96- and 384-well formats to study a wide range of targets by assessing different biological outcomes: Projects run at the DSP can use a wide range of readout technologies: Absorbance Fluorescence Fluorescence polarisation Luminescence FRET Alpha technology ELISA High Content Imaging Screening: screening platform + collaboration with the Advanced Digital Microscopy Facility.

GINYS-IRB-008

Open