Practical Fragments

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...

Transcription factors can be difficult drug targets, particularly those whose primary structure is a “leucine zipper” in which two α -helice...

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

Last year we highlighted a paper out of Novartis describing a fragment-to-lead story for interleukin-1 beta (IL-1β), a pro-inflammatory cyt...

Protein-protein interactions have a well-deserved reputation for being difficult to drug with small molecules. This is particularly true for...

Stabilizing protein-protein interactions is becoming increasingly popular, and not just for PROTACs . Nearly three years ago we highlighted ...

One of the talks at the Discovery on Target meeting last month described the discovery of small molecule inhibitors of IL17A, a pro-inflamm...

One of the more challenging protein-protein interactions targeted by drug hunters is the interface between the transcription factor NRF2 and...

The cytokine tumor necrosis factor α (TNFα) is a key mediator of inflammation and has long been a target for rheumatoid arthritis, Crohn’s d...

In FBLD – as in most areas of research – speed and efficiency are prized. The faster you can find quality fragments, the faster you can adva...

Stabilizing – rather than disrupting – protein-protein interactions is increasingly popular, particularly in the context of PROTACs and mol...

RAS family proteins are considered a holy grail of oncology research. Way back in 2012 we discussed a couple papers disclosing low affini...

Venetoclax , the second fragment-based drug to reach the market, binds to and blocks the activity of the anti-apoptotic protein Bcl-2, all...

Last week we highlighted molecules that inhibit the interaction between oncogenic RAS proteins and an activator protein, SOS1. This week c...

Last week we highlighted an example of fragments stabilizing a protein-protein interaction. This week continues the theme, with a paper p...

Despite the fact that the second FDA-approved fragment-derived drug targets a protein-protein interaction (PPI), these types of targets ha...

Six years ago we highlighted papers from Genentech and Steve Fesik’s group reporting fragments that bind to Ras-family proteins, which ar...

Three years ago we highlighted a paper from Astex describing the discovery of an extraordinarily weak fragment and its advancement to a du...