Practical Fragments

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...

Last week some 875 people attended the CHI Drug Discovery Chemistry ( DDC ) meeting in San Diego. I can’t do justice to the 40 or so present...

Last week we highlighted work out of Steve Fesik’s lab at Vanderbilt University about PLPro. This week we’ll highlight another paper just p...

The most successful drug against COVID-19, nirmatrelvir, targets the main protease of SARS-CoV-2. As we discussed just last year, this prot...

Since the invention of ligand efficiency ( LE ) more than two decades ago, scholars have been debating its strengths and weaknesses. And alt...