Practical Fragments

Four years ago we highlighted a fragment-merging approach targeting fat mass and obesity-associated protein (FTO), an RNA demethylase impli...

Ligand efficiency ( LE ) has been discussed repeatedly and extensively on Practical Fragments , most recently in September . Two criticisms ...

Back in 2023 we highlighted a computational fragment linking/merging approach which was used to find high nanomolar inhibitors of the SARS-...

Many readers of this blog will be familiar with KRAS, a mutant form of which was successfully targeted a few years ago by a covalent, fragme...

Synthetic lethality is a relatively new approach to treating cancer by targeting proteins whose inhibition is lethal to cancer cells that h...

Halogen bonds (or X-bonds) are one of the less appreciated protein-ligand interactions. As we discussed in 2022, the polarized nature of a ...

Ivermectin is a miracle drug. It cures infections caused by several types of parasitic roundworms, including those that cause river blindnes...

As our poll last year demonstrated, there is no shortage of methods to find fragments. But that doesn’t mean new approaches aren’t welcome,...

The CHI Discovery on Target ( DoT ) meeting was held last week in Boston. More than 850 people from 24 countries attended, 75% from industry...

Migraines are the third leading cause of disability worldwide. Although the pathology is complex, blocking the interaction of calcitonin gen...

Ligand efficiency ( LE ) was proposed more than two decades ago as “a useful metric for lead selection.” The concept is simple: divide the b...

Nearly a decade ago we highlighted a paper from Astex that exhorted chemists to develop new synthetic methodologies useful for fragment-bas...

Accurately and reliably predicting fragment binding modes would be preferrable to doing messy, expensive, and sometimes tedious experimental...

Kelch-like ECH-associated protein 1 (KEAP1) binds to nuclear factor erythroid 2-related factor 2 (NRF2), targeting it for degradation. Block...

The ten human fatty-acid binding proteins (FABPs) shuttle lipids around cells. As we noted several years ago, FABP4 and FABP5 are potential...

Although 2020 and 2021 were baleful exceptions, tuberculosis is normally the world’s deadliest infectious disease. The pathogen Mycobacteriu...

Last week we highlighted a new tool to computationally predict whether a molecule might aggregate, thereby causing false positives. This do...

Among the many types of artifacts that can fool screens and derail efforts to find leads, small colloidally aggregating molecules (SCAMs) a...