Target-Based Screening, Protein Expression and DMPK
Established around a single project in 2003, our drug discovery and development team has worked successfully with colleagues across the University on a diverse portfolio of therapeutic targets, advancing these towards successful translation.
The team possesses unique experience within the University context, covering protein biochemistry, assay development, in vitro screening, DMPK, in vivo efficacy models, medicinal chemistry and project management for toxicology and early clinical development. It has established effective relationships with a network of external advisors, industrial collaborators and contract research organisations.
Assay Development and Target-Based Screening
The core team has extensive experience in developing robust high throughput screening (HTS) assays to industry standards. Instrumentation is available for automated dispensing in HTS format (Tecan Freedom Evo, Thermo Multidrop) and for assays in a variety of formats, including fluorescence, absorbance, luminescence, scintillation proximity and LC-MS/MS (Tecan M1000 microplate reader, Molecular Devices Spectramax microplate reader, Perkin Elmer TopCount, Thermo TSQ Quantum, ABI Sciex 5500).
Protein Expression and Cell-Based Techniques
High throughput screening requires a robust source of target that is expressed in mammalian cells or in the form of isolated protein. The team is skilled in stable or transient expression of protein targets and the subsequent development of cell-based screens. The team has considerable experience of expressing proteins in E. coli, baculovirus and mammalian cells to express ‘challenging’ proteins. Equipment for protein purification is available (GE ÄKTA Protein Purification System) and links to structural biology are well established.
Drug Metabolism and Pharmacokinetics (DMPK)
A suite of in vitro DMPK assays has been developed to allow the rapid assessment of compounds during lead optimisation. These include CYP450 inhibition, plasma protein binding, microsomal stability, intrinsic clearance, metabolite identification and cytotoxicity assays. The team is skilled in the use of liquid chomatography-mass spectrometry/mass spectrometry techniques for the assessment of pharmacokinetic and pharmacodynamic parameters in rodents and are experienced in a range of in vivo disease models for the assessment of preclinical efficacy.
Uniquely in a university context, the team has proven experience spanning both drug discovery and development. We are thus able to advise and support projects at all stages of the drug discovery process, including medicinal chemistry, toxicology, manufacturing and clinical development.