Small Molecules

Innovative translational drug discovery & development from pre-clinical validation to proof of concept

The EATRIS Small Molecules platform supports the pre-clinical and clinical development of drug candidates, utilizing academic expertise around novel targets and molecular scaffolds. The platform offers 25 expert translational medicine institutions and has access to advanced screening facilities with innovative cell-based assays as well as integrated use of the latest biomarker techniques.

Alfredo Budillon
Co-chair
Small Molecules Platform
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Tailored animal models help shorten the time to in vivo proof of concept and study the mode of action of novel drug candidates and targets, supported by experts in pharmacology, medicinal chemistry, analytical chemistry and toxicology. In addition, crossover synergy is provided by the EATRIS Imaging & Tracing and Biomarker platforms to speed up small molecules development programmes to achieve early proof of concept all within one infrastructure.

Infrastructure and expertise:

  • Development of xenograft models for translational in vivo screening
  • Advanced screening using 3D cultures and primary cells
  • Access to patient-derived primary cells (e.g. tumor cells, and fibroblasts)
  • High throughput and (automated) high-content analysis compatible 3D cell cultures
  • Modified liquid-overlay culture for spheroid production
  • Flow cytometry read-outs to detect cell differentiation
  • Transcriptomic analysis of multi-drug resistance
  • Cellular screening for novel drug candidates (and drug combinations) including radiochemotherapy using X-rays
  • Studying the penetration of DNA de-methylating drugs in reporter cell spheroids
  • Application of pH microsensors for screening under extracellular acidosis conditions
  • Compliant handling of patient samples (i.e. signed informed consent and ethical approval)

ADME profiling:

  • Determination of chemical stability (non-enzymatic degradation), stability in biological fluids (plasma, saliva, gastric juice)
  • Assessment of passive absorption and permeability in the gastrointestinal tract
  • Identification of drug transporter substrates
  • Prediction of blood brain barrier permeability
  • Microsomal stability and drug plasma protein binding assays
  • Advanced mass spectrometry (MALDI) analysis of drugs and metabolites
  • 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

Toxicity profiling:

  • 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

Preclinical validation of nano medicines:

  • Nanoparticle formulation design and development
  • Nanocarrier characterisation (size, shape, distribution profile)
  • Enhanced drug delivery using peptides, conjugates and liposomal formulations

Early clinical development:

  • Experience in many disease areas, with particular strength in oncology, neurodegenerative disorders, cardiovascular disease and rare diseases
  • Support for clinical trial design, execution and analysis in clinical centres, including biostatistics and legal and ethical approval
  • Access to patient materials and cohorts
  • Close interaction with regulatory affairs and clinical experts (IMPD, clinical dossier, orphan drug designation, clinical expert opinions)
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