Poor metabolism and toxicity cause over 50% of all clinical failures of new drug candidates. While the P450 enzymes play a critical role in metabolism of many drugs by catalyzing the first step in their biotransformation, there is no effective technology to screen for drug candidates' interaction with purified human P450 isozymes. Such capability would provide early notice to drug discovery teams of potential pharmacokinetic problems, drug-drug interactions, and pharmacogenetic complications before entering into more expensive testing in animals or humans. To address the strong commercial interest in such technology,Phase II studies will focus on creating an absorbance-based, universally applicable assay for the six major P450s that allow prediction of in vivo pharmacokinetic parameters. PanVera made a significant technical breakthrough towards this goal in Phase I by developing the RECO(TM) assay, a novel in vitro system that overcomes the historical problems of using purified proteins for screening P450 enzymes. In Phase II, PanVera will use the RECO system to incorporate the key human P450 isozymes into a high throughput screening assay for rapid analysis of P450-dependent metabolism of large, diverse compound collections. Phase III efforts will focus on commercializing the assays through PanVera's extensive drug discovery research customer base.
New commercial applications from this research include: 1) non- radioactive, homogeneous, high throughput P450 screening assays to aid in drug discovery and 2) production of large amounts of purified P450 proteins for structure-function studies and synthesis of metabolites.
