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...

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...

Turning and turning in the widening gyre The falcon cannot hear the falconer…   In our small, annual counterweight to Yeats’ “ mere a...

Proteins can be remarkably dynamic, and, as we noted recently, different conformational states can reveal different pockets for small molec...

Many interesting proteins have flat, featureless surfaces, lacking the deep pockets in which small molecules usually bind. But structures ca...

Yesterday, on October 29, the US FDA approved asciminib (ABL001, from Novartis) for two subsets of patients with chronic myeloid leukemia ...

Screening fragments crystallographically is becoming more  common , especially as the process becomes increasingly automated . Not only doe...

Last year we described the discovery of asciminib , an allosteric inhibitor of the kinase BCR-Abl that binds in the enzyme’s myristoyl-bind...

Most drugs – and small molecule modulators in general – inhibit something, often an enzyme. Enzyme activation , on the other hand, is rare;...

Carbohydrates are ubiquitous in nature but largely ignored in drug discovery. This is because interactions between carbohydrates and protei...

Imatinib is the early poster child of personalized medicine. The drug famously works by binding to the mutant kinase BCR-ABL1, and its app...

Proteins in cells are constantly synthesized and degraded in a complex, highly regulated manner managed in part by the ubiquitin proteasome...

The year is done , and the darkness Falls from the wings of Night. As we've done since 2012 , Practical Fragments is ...