Highlights • PROTACs have become an established modality with examples reaching the
clinic. • PROTACs often breach “rule-of-5” limits, but oral bioavailability is achievable. • The …

This review promotes the value of isolated hepatocytes in modern Drug Discovery programmes
and outlines how increased understanding, particularly in the area of in vitro–in vivo …

During drug discovery and prior to the first human dose of a novel candidate drug, the
pharmacokinetic (PK) behavior of the drug in humans is predicted from preclinical data. This helps …

The aim of this study was to evaluate a unified method for predicting human in vivo intrinsic
clearance (CL int, in vivo ) and hepatic clearance (CL h ) from in vitro data in hepatocytes …

P450 cytochromes (P450) catalyze many types of oxidative reactions, including the conversion
of olefinic substrates to epoxides by oxygen insertion. In some instances epoxidation …

The intrinsic clearances (CL int ) of 50 neutral and basic marketed drugs were determined
in fresh human hepatocytes and the data used to predict human in vivo hepatic metabolic …

Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y 12
receptor antagonists and exploitation of their SAR is described. Modifications of the acidic side …

In this article approaches to predict human pharmacokinetics (PK) are discussed and the
capability of the exemplified methodologies to estimate individual PK parameters and …

Herein we report the optimization of a series of tricyclic indazoles as selective estrogen
receptor degraders (SERD) and antagonists for the treatment of ER + breast cancer. Structure …

A fully automated assay to determine the enzymology of drug oxidation by the major human
hepatic cytochrome P450s (CYPs; CYP1A2, -2C9, -2C19, -2D6, and -3A4) coexpressed …