Customer Application (system support)
The Role of Automation and Robotics in High Throughput ADME Profiling of Potential Drug Candidates (Cytochrome P450 Analysis on a Core System)
K. M. Jenkins Ph.D., R. Angeles, M. T. Quintos, M. Wright, R. A. Rourick,
and D. B. Kassell
DuPont Pharmaceuticals Research Laboratories
DuPont Pharmaceuticals - www.dupont.com
Early determination of pharmaceutical properties can serve as predictors of a compound's likely development success. Therefore, implementation of high throughput ADME Tox assays which address absorption, metabolism, and physico-chemical properties may serve to minimize discovery to market attrition. In effort to meet the throughput demands of parallel synthesis, an integrated solution for ADME Tox assays has been established which incorporates a SAGIAN™ Core System for the development of both metabolic stability in human liver microsomes (HLM) and Ctyochrome P450 (CYP) inhibition. This automated solution has been allowed an increase in capacity, throughput and reliability for both ADME Tox assays.
The HLM assay utilizes a Multimek™ 96 channel pipettor for liquid handling. The analysis plates are transferred off-line for final analysis using an ultra-high throughput parallel LC/MS approach. The CYP inhibition method uses a combination of liquid handlers and a fluorescence plate reader to perform a single concentration profile assay for 88 compounds.
The system represents a fully integrated approach in support of high throughput ADME evaluation in a drug discovery environment. The core system concept creates a plug-and-play approach, which combines a series of modular stations to build a robotic system, which is flexible upgradeable, and easily re-configurable when assays change or are newly developed. The application of these strategies as a means of assessing metabolic stability and CYP inhibition of our combinatorial libraries is presented in the following presentation: The Role of Automation and Robotics in High Throughput ADME Profiling of Potential Drug Candidates.
Features
- Automation of screening assays is key for large number of samples.
- Platforms are consistent and reproducible.
- Beckman Coulter platforms are flexible and easy to setup.
- Open architecture of Beckman Coulter platform allows easy integration of additional devices.
- SAGIAN Core system is cost effective as compared to multiple standalone workstations
* All trademarks are the property of their respective owners. Where applicable, the PCR process is covered by patents owned by Roche Molecular Systems, Inc., and F. Hoffman-LaRoche, Ltd.
