Beyond-Rule-of-Five Compounds Are Not Different: In Vitro-In Vivo Extrapolation of Female CD-1 Mouse Clearance Based on Merck Healthcare KGaA Compound Set.

ABSTRACT: Background: Extrapolation of intrinsic clearance from in vitro systems such as liver microsomes or hepatocytes is an established approach to predict clearance in preclinical species and in humans. A common discussion in the literature is whether the predictive accuracy of such extrapolations is influenced by the chemotype and whether these methods are also applicable to compounds studied in early drug discovery programs. Compounds in such programs are frequently lipophilic and show low solubility and low free fraction in plasma, which may pose challenges to the extrapolation of clearance different from those of the final clinical candidates. A similar discussion has been raised about compounds residing beyond the traditional small-molecule property space, such as PROTACs© and other

SUBMITTER: Maurer CK 

PROVIDER: S-EPMC12029992 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature