BioSeek: Secondary Activity of an Adrenergic Receptor Antagonist Bridging the Gap from In Vitro to In Vivo

BioSeek: Secondary Activity of an Adrenergic Receptor Antagonist
Bridging the Gap from In Vitro to In Vivo
Version:
V1

Year:
2013

THE CHALLENGE
The client was a global pharmaceutical company interested in adding therapeutics for benign prostatic hyperplasia (BPH) to its development pipeline, searching for opportunities outside the currently approved classes of BPH drugs.

Certain adrenergic receptor (AR) antagonists were already marketed to treat the urinary retention symptoms of BPH. Additional observations suggested that some of these compounds may have other beneficial effects, such as delaying progression of the underlying prostatic hyperplasia, through mechanisms that were not clear. The client was investigating the pharmacology of these drugs to discover possible new mechanisms for treating BPH

The challenge was to choose experimental models that could inform physiologically relevant hypotheses. The client’s strategy was to initially search broadly for new mechanisms to treat BPH. They had employed many panels of biochemical and cell-line based assays to identify new targets or pathways impacted by one particular AR antagonist, but these assays did not yield definitive results. Furthermore, results from these studies may have missed or overlooked relevant in vivo mechanisms. The client needed an assay system that filled the gap between simple cell lines and in vivo models, and yet was comprehensive enough to cover multiple mechanisms.