Practical Fragments

Epigenetic writers such as histone acetyltransferases (HATs) control gene expression, which often goes awry in cancer. The gene encoding the...

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

Kinases hold a special place in fragment-based drug discovery. Vemurafenib , the first approved FBDD-derived drug, targets a kinase, as do m...

COVID-19 is deservedly engaging most of our collective mindspace when it comes to infectious diseases. Unfortunately, plenty other threats...

Ligand deconstruction, in which a larger molecule is dissected into component fragments that are subsequently optimized, can be useful for...

Earlier this year we highlighted a paper from Novartis in which ligand deconstruction was used to deconstruct an HTS hit against the epige...

Sir James Black famously said that the best way to find a new drug is to start with an existing one. A drug not only has to bind to a targe...

Ligand deconstruction is a strategy for early-stage drug discovery in which a known hit is dissected into component fragments and one or m...

This past July Practical Fragments was devoted almost entirely to bromodomains , an important type of epigenetic protein. Protein lysine m...

Epigenetics involves turning genes on or off without changing their sequence. This often relies on modifications to proteins or DNA that a...

Ligand efficiency ( LE ) is one of the more controversial topics we cover at Practical Fragments . One critic asserted – incorrectly – th...

Since the advent of imatinib , kinase inhibitors have become a thing in drug discovery, with more than two dozen already approved. Indeed, ...

Say you have a protein target, and you want to know whether you will be able to find small molecules that bind to it. A fragment screen can...

Last week we highlighted a paper from Chris Johnson and collaborators at Astex and Janssen in which they used fragment-growing to develop ...

People often ask what a fragment is.  I like to paraphrase Justice Potter and say that it is like pornography; it is in the eye of the beho...

The year is spinning to an end, and as we did in 2013 and 2012 , Practical Fragments is looking back on notable events as well as reviews...

One of the more exciting phenomena in fragment-based approaches is synergy (or superadditivity), in which the binding energy of linked fra...

Recently we highlighted a paper in which enzyme substrates were deconstructed into component fragments and tested against an enzyme with u...

Ben Perry brought up an interesting question in a comment to a recent post about fragments that bind at a protein-protein interface: “At wh...

Protein-protein interactions (PPIs) are some of the tougher targets in drug discovery: they often have relatively flat interfaces that lack...