Target Identification & Validation
We provide many different approaches to look for drug target such as:
- Gene association studies (Genomics)
- Biomarkers (Proteomics)
- Imaging
- Cellular models
- Transgenic animals
- Tissue expression studies (Histology – Molecular Imaging)
- Biochemical pathway studies
Target to hit
- Chemical library (>5.000 in house compounds available for biological screening)
- Organic synthesis of small molecules & heterocyclic compounds
- Drug hemisynthesis from natural products
- Small to large scale compound purification
- Chiral resolution of racemic compounds
- Determination of physicochemical properties and complete characterization of organic compounds by spectral and elemental analyses
- Bio-guided isolation and structural determination of natural substances
- Preparative isolation of natural products at the gram scale (prepHPLC, prepCPC, prepTLC)
- Lab scale extraction of natural products
- Our Robotein Platform encompasses an Octet system that allows high-throughput analyses of protein interactions in 96- and 384-well microplates. It enables real-time and label-free determination of affinity, kinetics and concentration. This makes it highly suitable for the characterization of drug candidates.
- Our GIGA imaging platform encompasses a Becton Dickinson’s (BD) Pathway 855 High-Content Bioimager, which is a high performing imaging solution for live or fixed cell samples combining image quality, flexible image capture and live-cell analysis.BD Pathway system provides fluorescence intensity measurements, kinetic imaging and morphological analysis, including sub-cellular imaging. Images can be captured in either confocal or wide field mode to deliver high-resolution images for subsequent analysis.
Hit to lead
The GIGA focuses on the study of membrane receptors with a particular interest in G protein coupled receptors of unknown or elusive function.
The lab has a large expertise in:
- Development of original in vitro/ex vivo assays for the identification of active compounds
- Molecular cloning, epitope-tag fusion and mutagenesis of receptors/protein of interest
- Calcium assays
- cAMP measurement
- Resonance Energy Transfer technology (BRET and FRET)
- Co-Immunoprecipitation
- Critical assessment of existing assays for use in screening setting
- Elucidation of active molecule mechanisms and signaling pathway
- Discovery of original compounds modulating a protein/target
- Complete pharmacological profile of active molecules (pharmacodynamics)
- Analysis of signal pathways
- Targeted mutagenesis for binding pocket determination
- Receptor localization and trafficking
- Receptor tissue expression
- Chemical library screening (medium throughput)
- Determination of chemical stability (non-enzymatic degradation), stability in biological fluids (plasma, saliva, gastric juice)
- Assessment of passive absorption and permeability
- Identification of drug transporter substrates
- Prediction of blood brain barrier permeability
- Evaluation of metabolic stability (Microsomal Stability, Plasma Stability, Hepatocyte Stability)
- Protein Binding Assays (plasma, microsomal, brain)
- CYP profiling and inhibition
- Advanced mass spectrometry analysis of drugs and metabolites (identification and resolution of chemical structures)
- Quantitative determination of the distribution in organs and tissues of small rodents by LC-MS
- In silico prediction and PK/PD modeling of human ADME profile
- Good Laboratory Practice (GLP) compliant toxicity studies in mice, rats or rabbits
- Extended single dose (microdose) toxicity studies with hematology, clinical
- Chemistry, necropsy, and histopathology data
- Neurotoxicity, cardiotoxicity (ECG, BP) and respiratory toxicity
- 28-days or 90-days repeated toxicity studies with non-compartmental toxicokinetics
- Design of preclinical safety studies for authorization
- Local clinical trial centre to cover phase I and II clinical studies jointly with University Hospital of Liège (close interaction with clinical experts)
- Pharmacokinetic assessment in human
- Metabolism assessment with identification of drug metabolites in human (in various sample matrices)
- Comparison of drug biotransformation in human and animal
- Identification of structural features: analysis of relationships of drug structure and biological responses to understand target and untargeted drug effects.
- Degradation products identification or impurities profiling of active pharmaceutical ingredients and drug products
- Bioanalysis of natural or xenobiotic components
- Metabolism elucidation of food supplements
- Biomonitoring of oxidative stress biomarkers
- Evaluation of formulation and drug delivery technologies