Practical Fragments

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

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

Four years ago we highlighted a fragment-merging approach targeting fat mass and obesity-associated protein (FTO), an RNA demethylase impli...

Migraines are the third leading cause of disability worldwide. Although the pathology is complex, blocking the interaction of calcitonin gen...

Last week we highlighted a protein-detected NMR method that does not require expensive and sometimes difficult isotopic labeling of protein...

At the end of 2023 I mentioned that a paper by Dean Brown listed berotralstat as a fragment-derived drug. Readers will notice this molecule...

Machine learning (or, for investors, artificial intelligence) has received plenty of attention. To be successful you need lots of data. If y...

Practical Fragments has written frequently about hot spots , regions on proteins that are predisposed to bind ligands such as drugs. Determ...

Practical Fragments has written several times about “ hot spots ”: regions on proteins where small molecules and fragments readily bind. Kn...

The three members of the inositol hexakisphophate kinase family are potential targets for a wide range of diseases, from Alzheimer’s to canc...

Protein-detected NMR first enabled fragment-based lead discovery way back in 1996, but improvements in crystallography have now allowed syn...

Scientists generally want structural information when a project begins, and ideally that structural information comes from crystallography....

The receptor tyrosine kinase AXL has been implicated in multiple cancers, and more recently as a possible target for COVID-19. The protein h...

Earlier this year we highlighted a fragment optimization success story against a G protein-coupled receptor (GPCR) which made no use of str...

Advancing fragments in the absence of structural information has a reputation for being so challenging that some people do not even attempt ...

Mitogen-activating protein kinase-interacting kinases 1 and 2, or MNK1 and MNK2, are implicated in several cancers while seeming to be disp...

Good things come in threes, and since our last two posts have covered covalent fragments, we thought we’d continue the theme with two mor...

Just over a year ago we highlighted work out of A*STAR describing a series of inhibitors for the cancer target protein kinase C iota (PKC-...

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

It’s been a while since the last installment in our “getting misled” series. One of the key issues with crystallography is that ligands ar...