THE CAPABILITIES OF THE MOULDER CENTER FOR DRUG DISCOVERY RESEARCH AT THE TEMPLE UNIVERSITY SCHOOL OF PHARMACY
We synthesize, purify, and study organic molecules. Our chemistry laboratories are designed to handle mg to kg scale small molecule synthesis. Parallel synthesis platforms are also available for the preparation of either diversity driven or focused libraries of 10s to 1000s of compounds on 10 – 100 mg scale. We handle large scale synthesis to meet the needs of PK studies, in vivo animal studies, and CGMP production.
The Biotherapeutics Laboratory brings state-of-the-art discovery capabilities for work on protein-based drugs to the Moulder Center. Drawing on over 30 years of academic and industrial experience in prokaryotic, eukaryotic and viral molecular genetics, heterologous protein expression and therapeutic antibody discovery and engineering, we utilize phage display technology as our primary protein discovery platform. We are the only academic group in the world with access to the “Ylanthia” Fab display phage library, a powerful industrial-quality human antibody discovery platform.
We handle expression profiles, protein identification, posttranslational modification, characterization, isolation of individual cells from tissues, protein and peptide separations, capillary electrophoresis, and multidimensional protein identification (MudPIT). Our facility is capable of generating high fidelity data for biomarker discovery, drug targets and studies on the pathogenesis of disease. Our proteomics laboratory and faculty provide accessible proteomics capability for biological and biomedical research.
Solid Phase Peptide Synthesis
We conduct peptide synthesis and purification, as well as identification and characterization of proteins from recombinant or biofluidic sources, using state-of-the-art Solid Phase Peptide Synthesis (SPPS ) equipment, including the CEM Liberty 1 Microwave Peptide Synthesizer.
In Vitro Assay Development and Screening
Our high throughput screening capabilities are built around two Janus Automated Workstations (Varipsan and MDT) capable of supporting 96-well or 384-well platforms. The system supports multiple in vitro and cellular assay paradigms for the study of enzymes, receptors, ion channels and transporter proteins.
High throughput screening is supported by a 40,000 member small molecule diversity-based screening library which includes linear and cyclic peptides as well as the Prestwick 1,200 member library of FDA approved drugs. The Moulder Center recently licensed and implemented the Dotmatics Informatics Platform (Dotmatics, Ltd) to support the chemical database, high throughput screening data management, structure activity relationship (SAR) analysis, and data visualization.
In Vivo Assay Development and Screening
- Micro dissection
- Behavioral assessment
- Conditioned place preference
- Analgesia and tolerance
Ex Vivo Assay Development and Screening
- Radio ligand
- Homogenate binding
- Rubidium efflux
- Neurotransmitter release
- Receptor profiling
- Drug affinities
- Functional responses
- Subunit composition
- Quantification and distribution
- Protein and neuron characterization
- Western blotting
- Synaptosomal preparations
Other Specialized Capabilities
- Pharmacogenomic Analysis of SNPs
- Copy Number Variations
- Cell-based assays
- caspase activation
- cell viability
- In-vitro metabolism
- Pre-clinical PK
In Vitro ADME and Pharmacokinetics
We are equipped to provide a wide range of in vitro ADME/PK studies, drug metabolism studies and in vivo Pharmacokinetics (PK) studies in support of drug discovery programs.
In Vitro Assays
- Microsomal Stability – Human and preclinical species
- Hepatocyte Stability – Determine direct conjugation or metabolism by aldehyde oxidase
- Unbound fraction assays – Equilibrium dialysis and LC/MSMS analysis and interpretation
- CYP inhibition assays - CYP3A4, CYP2D6 and CYP2C9
- Permeability assays – CACO-2 and MDCK for correlation with absorption and BBB
- Metabolite ID – Tissue preparations, expressed enzymes and LC/MSMS identification
In Vivo Assays
- Preclinical Pharmacokinetics – Mouse and rat studies (IV and oral) to determine
- Volume of distribution
- CNS Penetration - Mouse and rat with SC, IP, or IV administration