Library Screening for Stability

The advent of high throughput techniques have had a profound effect on pharmaceutical companies and the drug discovery process worldwide. The numbers and types of compounds available for elucidation have increased by orders of magnitude. This unprecedented capability has greatly expanded the number of compounds in a pharmaceutical company's library. While new methods may be the answer to the age-old problem of rapid compound generation and modification, it has also led to the production of many compounds that possess undesirable chemical properties for use as a pharmaceutical. The need has arisen to develop quick and accurate tests to aid in the decision to remove these compounds from a chemical library.

A key parameter for the use of any compound as a drug is that of its inherent chemical stability. This stability can include everything from a measurement of a compound's stability under oxidative conditions, to the testing of a compound under artificial "forced degradation" conditions.

ESA has applied its unique products and expertise in bioanalytical detection to provide the tools to easily and quickly test even early stage compounds for their oxidative stability. ESA’s CoulArray® electrochemical system can provide researchers with a path to quickly and easily eliminate "problem" compounds with undesirable stability characteristics by testing the inherent stability of virtually any compound for oxidative degradation. ESA systems can also provide researchers with important new information in regards to a compound's expected degradation pattern and degradation products. ESA systems are quick and easy to use with almost any analytical equipment, and require minimal amounts of compound for analysis.

Identify Problem Compounds Quickly and Easily

In the biophysical characterization laboratory the ability to make quick and accurate decisions about a compound is paramount. The ESA CoulArray Electrochemical system is capable of:

• Quickly and accurately predicting a compound’s oxidation patterns
   
• Identifying degradation products
   
• Identifying "susceptible" molecules or functional groups for oxidative metabolism

This enables laboratories to:

• Easily identify potential "problem" compounds from libraries and assays
   
• Include additional physiochemical information on compounds
   
• Predict a compound's oxidative stability with minimal compound consumption

The CoulArray Electrochemical system easily integrates with most existing bioanalytical and data analysis systems.

Figure 1. Oxidative Stability of Compounds. Various compounds were passed through CoulArray electrochemical cells and their stability to oxidative degradation was measured. Compounds known to be oxidatively labile, are shown to oxidize at low potentials. Compounds known to be stable, show oxidation only at higher potentials.

Figure 2. Rank Ordering of Compounds by Oxidative Stability. Various compounds were tested and their relative stabilities were ranked by electrochemical reaction.

An assessment of a compound’s oxidative stability early in the development process can be of great value. In addition to providing primary information about stability, these data aid in the interpretation of subsequent testing. When screening against specific targets, it is important to know about the stability of the compound to interpret the results.

Source: ESA - A Dionex Company