BioProject

A genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. More...

A genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis. Overall design: 52 samples were initially run, 45 passed QC and were analyzed, samples were run in 4 independent replicates and were treated with either vehicle, R547 at the IC50 concentration, R547 at the IC90, or R547 at 3 times the IC90. Samples were harvested at 2, 6, and 24 hours post treatment. Additionally, untreated time zero samples were analyzed as a further control Less...