PamGene - Nuclear Receptor Compound Profiling and Kinase Compound Profiling

PamGene's three-dimensional PamChip® microarrays offer a new alternative for pharmaceutical companies’ kinase and nuclear receptor drug discovery programs. Their ability to predict future successes from past experience is one area that is proving to be particularly appealing to researchers.

The keys are PamGene's tyrosine and serine / threonine kinase PamChip® microarrays for cell lysate-based applications and nuclear receptor PamChip® microarrays. Companies can use the arrays to analyse their past portfolio of successful and unsuccessful compounds, leads and drugs. By comparing past and present patterns, molecules can be categorized.

COMPANION DIAGNOSTICS: PREDICTING IF CANCER DRUGS WILL WORK BEFORE TREATMENT

New biomarker development, based on changes in kinase activity, is at the root of PamGene’s drive towards making ‘companion diagnostics’ a reality. Using these new biomarkers, PamGene’s technology platform can measure the effect of a drug on kinase activity in the patient’s own tissue (a biopsy) prior to treatment. In other words, strong hints about the likelihood of a cancer drug's effectiveness in that patient can be obtained before initiating treatment. This has important implications for patient treatment, clinical trials, and for the agencies that finance drug therapy.

NUCLEAR RECEPTOR COMPOUND PROFILING AND KINASE PROFILING

PamGene’s PamChip® microarrays can simultaneously measure potency, efficacy and selectivity of kinase or nuclear hormone receptor drug candidates in one experimental run. The chips contain content that is carefully selected by academic, biotech and pharma partners, and they are used by companies including Merck Research Labs, West Point, PA (nuclear receptors) and Johnson & Johnson PRD, Beerse, Belgium, (kinases).

This type of compound profiling improves early selection procedures, thereby increasing the right molecule's chance of making it through the drug development process.

TYROSINE KINASE PAMCHIP® ARRAYS

By analysing all your compounds’ phosphorylation patterns on PamGene's tyrosine kinase PamChip® arrays, you can build up a record of what works and what doesn’t.

Tyrosine kinase PamChip® arrays allow you to:

• Differentiate between promising compounds and problematic compounds early in the secondary screening process
• Map biopathway inhibitor interactions
• Send your compounds into clinical trials with more confidence

The tyrosine kinase PamChip® is ideal for unravelling kinase pathways and ranking tyrosine kinase inhibitors based on selectivity and potency. These arrays are suitable for assays using cell lysates or recombinant kinases. Each array consists of 144 relevant and carefully selected peptides, each peptide consisting of a putative phosphorylation site.

SERINE / THREONINE PAMCHIP® ARRAYS

These arrays are intended to unravel the pathways of serine and threonine kinases. Serine and threonine kinase inhibitors are ranked based on selectivity and potency.

These arrays are suitable for assays using cell lysates or recombinant kinases. They contain 196 relevant and carefully selected immobilised phosphopeptides, representing serine and threonine kinase substrates.

NUCLEAR RECEPTOR PAMCHIP® ARRAYS

Nuclear Receptor (NR) PamChip® arrays are ideal if you are looking for potent compounds that are selective only for your target-specific interaction. With PamChip® microarrays for NR-based research, you can test thousands of conditions in one single experimental run and immediately rank your compounds based on potency, efficacy and selectivity. Each of the arrays consist of 48 relevant and carefully selected peptides, each representing the binding motifs of nuclear proteins.

PamGene's unique real-time kinetic read out (measurement over time of the binding of the nuclear receptor to the co-regulator peptide) gives:

• A full kinetic overview of your NR target/compound reaction with all of the nuclear proteins rather than just a snap-shot or end-point information
• Multiple data points enabling curve fits to be made, leading to accurate determination of initial binding rates
• Robust results due to full assay automation and easy, automated removal of outliers

FOUR-ARRAY SYSTEMS FOR PROCESSING PAMCHIP 4 ARRAYS

PamGene offers a range of instrumentation to meet your research and development requirements. The PamStation® 4 and the PamStation® 12 are fully-automated four-array systems designed for processing PamChip® 4 arrays.

Key attributes:

• Fully integrated incubation, washing and image acquisition (up to six fluorescent channels)
• Suitable for nucleic acid and protein analysis
• Can alter temperature on-line (20°C - 80°C) and watch experiment progress in real-time; ideal for generating melting and binding curves
• Real-time detection offers unique capability of generating kinetic data on enzyme/substrate interactions

SCREENING APPLICATIONS

This fully-automated and integrated PamStation® 96 system is designed for processing PamChip® 96 plates. It is ideal for high throughput, microarray-based screening applications.

Key features:

• Incubation, washing and imaging capability (up to four fluorescent channels)
• Up to 96 arrays (one plate) can be analysed at one time
• Up to 48 plates can be processed per day
• Can alter temperature on-line (20°C - 80°C) and watch experiment progress in real-time; ideal for generating melting and binding curves

BIOMARKERS

PamGene is involved in a number of collaborations involving multiplex biomarker discovery using cell lysates from clinical material such as blood, primary tumour material and tissue biopsies.

The phospho-fingerprinting method, which was evaluated and presented by Wyeth at the annual Drug Discovery Technology conference in Boston in August 2006, is one of PamGene’s most advanced technologies in this field.