A principal challenge in the discovery of proteolysis targeting chimeras (PROTACs) as oral
medications is their bioavailability. To facilitate drug design, it is therefore essential to …

Increasing disease-related proteins have been identified as novel therapeutic targets.
Macrocycles are emerging as potential solutions, bridging the gap between conventional …

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

Abstract Cyclin-dependent kinase 9 (CDK9) is a promising therapeutic target in multiple
cancer types, including acute myeloid leukemia (AML). Protein degraders, also known as …

Molecular chameleonicity may enable compounds to compensate for the unfavorable ADME
properties typically associated with complex molecules, such as PROTACs. Here we present …

Chameleonicity (the capacity of a molecule to adapt its conformations to the environment)
may help to identify orally bioavailable drugs in the beyond-Rule-of-5 chemical space …

Despite the increased use of computational tools to supplement medicinal chemists'
expertise and intuition in drug design, predicting synthetic yields in medicinal chemistry …

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

Achieving oral bioavailability with Proteolysis Targeting Chimeras (PROTACs) is a key
challenge. Here, we report the in vivo pharmacokinetic properties in mouse, rat, and dog of …

Abstract Proteolysis-targeting chimeras (PROTACs), as heterobifunctional molecules, have
garnered significant attention for their ability to target previously undruggable proteins. Due …