Probing the links between in vitro potency, ADMET and physicochemical parameters.

ABSTRACT: A common underlying assumption in current drug discovery strategies is that compounds with higher in vitro potency at their target(s) have greater potential to translate into successful, low-dose therapeutics. This has led to the development of screening cascades with in vitro potency embedded as an early filter. However, this approach is beginning to be questioned, given the bias in physicochemical properties that it can introduce early in lead generation and optimization, which is due to the often diametrically opposed relationship between physicochemical parameters associated with high in vitro potency and those associated with desirable absorption, distribution, metabolism, excretion and toxicity (ADMET) characteristics. Here, we describe analyses that probe these issues further using

SUBMITTER: Gleeson MP 

PROVIDER: S-EPMC6317702 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature