Developing orally bioavailable drugs demands an understanding of absorption in early drug
development. Traditional methods and physicochemical properties optimize absorption for …

Targeted protein degradation by PROTACs has emerged as a new modality for the
knockdown of a range of proteins, and, more recently, it has become increasingly clear that …

Conformational flexibility has been proposed to significantly affect drug properties outside
rule-of-5 (Ro5) chemical space. Here, we investigated the influence of dynamically exposed …

The rule of 5 (Ro5) is a set of in silico guidelines applied to drug discovery to prioritize
compounds with an increased likelihood of high oral absorption. It has been influential in …

Polar molecular surface area provides a valuable metric when optimizing properties as
varied as membrane permeability and efflux susceptibility. The EPSA method to measure …

New chemical modalities in drug discovery include molecules belonging to the bRo5
chemical space. Because of their complex and flexible structure, bRo5 compounds often …

To obtain new oral drugs in the beyond rule of five space, PROTACs among others,
molecular properties should be optimized in early drug discovery. Degraders call for design …

An ab initio conformational analysis of oral beyond Rule of 5 (bRo5) drugs was
complemented with measured permeability and logP (octanol) to derive design principles …

Solubility optimization is a crucial step to obtaining oral PROTACs. Here we measured the
thermodynamic solubilities (log S) of 21 commercial PROTACs. Next, we measured BRlogD …

Drug discovery for difficult targets that have large and flat binding sites is often better suited
to compounds beyond the “rule of 5”(bRo5). However, such compounds carry higher …