Practical Fragments

Last week we highlighted how NMR-based fragment screening was able to identify cryptic pockets on a small protein. Experimental methods are...

We’ve written previously about the concept of synthetic lethality, in which changes to one protein make cancer cells more dependent on anot...

RNA helicases present an intriguing but challenging opportunity for drug discovery. Their importance for cell growth makes them attractive c...

Most methods to characterize protein-ligand binding interactions have drawbacks. Crystallography, obviously, requires your protein to crysta...

Protein tyrosine phosphatase 1B (PTP1B) is a long-standing target for diabetes and other diseases. But as we’ve written previously, it is c...

Back in 2009 we highlighted a paper, “Escape from flatland,” suggesting that molecules with higher fractions of sp 3 -hybridized (ie, non-a...

Earlier this year we highlighted a study that compared the affinities of kinase inhibitors for isolated proteins vs those same proteins in ...

Differential scanning fluorimetry (DSF), also known as a thermal shift assay, is one of the most common techniques for fragment screening ac...

Last month Practical Fragments wrote about make-on-demand libraries, such as those offered by Enamine. We’ve also written about fluorine-...

We're half-way through 2026, but there are still some good events ahead. And 2027 is already starting to take shape. September 14-16: Fr...

Fragment linking is a compelling approach to advancing fragments, but, as our poll from several years ago showed, it often works better in ...

Exactly 17 years ago, I  highlighted a paper from Brian Shoichet’s lab in which he hypothesized that only tiny regions of chemical space ar...

Last week we highlighted a study in which an attempt to optimize a covalent fragment led to a non-covalent fragment that bound in a differe...

The seven members of the 14-3-3 family act as “hub proteins” that bind to other proteins, bringing them together or affecting their subcellu...

Just over two years ago we highlighted a new clinical candidate targeting WRN, a covalent inhibitor then called VVD-133214. An open-access ...

Last week we described the discovery and early optimization of noncovalent inhibitors against the the DNA helicase WRN, an interesting onco...

Werner syndrome helicase, or WRN, is an interesting target both for its biological mechanism and its flexible structure. Two years ago we hi...

It’s been a while since our last “getting misled by crystal structures” post . That one described unrecognized conformational heterogeneity ...

Despite its ubiquitous use as a model organism, Escherichia coli causes nearly a million deaths each year worldwide. Antibiotics provoke ra...