Targeted protein degradation (TPD) is an emerging therapeutic modality with the potential to
tackle disease-causing proteins that have historically been highly challenging to target with …

Artificial intelligence (AI) tools are increasingly being applied in drug discovery. While some
protagonists point to vast opportunities potentially offered by such tools, others remain …

Two decades have passed since the rule of five ushered in the concept of “drug-like”
properties. Attempts to quantify, correlate, and categorize molecules based on Ro5 …

Proteolysis targeting chimeras (PROTACs) are heterobifunctional compounds with
molecular weights and other properties that lie outside the classic 'rule-of-five'space …

Drug design is central to the discovery of a new medicine, as the drug molecule embodies
the therapeutic hypothesis of a drug discovery program and encodes the properties …

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 …

Optimization of compound lipophilicity is a key aspect of drug discovery. The aim of this work
was to compare the lipophilicity modulations induced by 16 distinct known and novel …

Physicochemical descriptors commonly used to define “drug-likeness” and ligand efficiency
measures are assessed for their ability to differentiate marketed drugs from compounds …

The rule of 5 was designed to estimate the likelihood of poor absorption or permeation,
noting the impact of poor solubility. This Perspective explores the impact of various …

Fluorination is commonly employed to optimize bioactivity and pharmaco-kinetic properties
of drug candidates. Aliphatic fluorination often reduces the lipophilicity (log P), but …