High throughput physicochemical profiling
- beyond logP and PAMPA
Todays compound development, QSAR and ADME/tox require the availability of the true molecular scale properties of the compounds. In this respect computational methods are already in full use. However, the level of sophistication of the computational techniques is in striking contrast to the cumbersome and at the best descriptive experimental methods, which until now have been available for physicochemical profiling. No longer so: Kibron Delta-8 analyzer now brings a whole new dimension to your R&D. More specifically, Delta-8 makes surface activity profiling, i.e. the characterization of the amphiphile properties of compounds, a real, practical utility. Further, surface activity profiling by Delta-8 is a true HTS technique, meaning that it can be adapted in lead optimization and even in the hits-to-leads phase.
In addition to existing methods, such as logP, Lipinski rule of five and PAMPA, profiling of TSA (true surface area), Kaw (vectorial lipophilicity), CMC (critical micelle concentration) and surface pKa (ionization constant) are important indicators in predicting blood brain barrier permeation and fraction absorbed. And this is just the tip of the iceberg. Amphiphilicity profile predicts, if the compound is toxic or potentially irritating, for example.
Additionally to PLD screening, the Kibron Delta-8 high throughput analyzer provides these key parameters, easily and by true measurements. The Delta-8 analyzer yields the mechanistic reason why a compound does not pass through the lipid bilayer, thus giving directions for improvements of molecular structures in QSAR.
“The results indicate that surface activity profiling can be used to distinguish between poorly and well absorbed drugs.
The use of the novel multi-channel micro tensiometer provides a suitable screening technique in terms of both accuracy and throughput”.
K. Kiehm, M. Brewster, J. Peeters, and J.B. Dressman
Estimating intestinal permeability by surface activity profiling.
In AAPS Annual Meeting and Exposition, Nashville, November 6-10, 2005.
