In vitro ADMET profiling
A complete understanding of the relationship between in vitro and in vivo results of bio-active molecules is still elusive. Nonetheless, in vitro studies can serve as adequate tests to predict the in vivo properties of a compound. This is done by a number of in vitro assays that allow the prediction of Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) characteristics of such compounds.
In the process of compound optimization, which is a multidimensional, iterative process of design, synthesis and testing, ADMET data support the selection of compounds having the desired characteristics to advance to downstream study phases. Additionally, these data can guide the design of downstream in vivo studies.
List of in vitro ADMET assays carried out at Polyphor
- Cytotoxicity (2 cell lines)
- Lipophilicity (logD, logP distribution coefficients)
- Protein binding
- Permeability (Caco2, Pampa)
- Gastric and intestinal stability
- Metabolic stability in plasma
- Metabolic stability using liver or gut microsomes, or hepatocytes
- Metabolizing enzyme (Cyp450) inhibition