Using Conformetrix's Technology

 

Drugging GPCRs & ion-channels

(and other intractable therapeutic targets)

Conformetrix technology finally offers a viable alternative to HTS and conventional structure-based approaches to discovery. An accurate 4D-structure of the natural ligand for ANY protein target provides a sufficiently accurate blueprint for designing NCEs and can be obtained in a fraction of the time of x-ray crystallographic data.

 

Virtual screening

Compared to purely theoretically derived 3D-structures, an accurate experimentally determined ligand structure is far more likely to provide high-value virtual hits. Typically our hit rates from completely unbiased virtual compound libraries are 10 - 20%.

 

Hit characterisation

It is often extremely difficult to identify common pharmacophore motifs amongst groups of unrelated hit chemistries, irrespective of whether they've been selected in silico or in vitro. Conformetrix structures provide a means of quickly and simply getting to this key information.

 

Lead optimisation / QSAR

Conformetrix can bring accurate 3D-data to any medicinal chemistry problem. By focusing R&D effort on the key bonds and functional groups that will have the most impact on potency and selectivity, we can increase both the speed and productivity of drug design cycles.

 

This is true even where a substantial amount of co-crystal data is available, as data on a bound ligand in the active site only shows you where you want to go with a new drug chemistry. It says nothing about where else a particular ligand might be going, or indeed how likely it is to adopt a specific geometry. This wider knowledge of ligand dynamics is only accessible with Conformetrix technology.

 

Improving specificity

A 4D-structure makes it easy to identify specific bonds that are sub-optimal in a lead compound: either bonds that have more than one preferred geometry when only a single geometry is required or bonds where the geometry is skewed away from the precise bioactive configuration. Armed with this insight it becomes relatively straightforward to suggest new ways to improve a particular lead series or to tune bond chemistries away from off-target effects.

 

IP protection / Competitor drug analysis

The information provided by Conformetrix structures is uniquely powerful at informing IP protection strategies: determining where modifications can usefully be made and helping Medicinal Chemists to focus in on those derivatives and patent claims which are likely to be of most value.