C4X Discovery has developed pioneering methods for routinely determining single-crystal structures on sub-milligram quantities of material, allowing us to measure and use this complementary conformational data very early in our programmes. In this report, we grow large crystals of two polymorphs of tolfenamic acid and solve their structures to high enough resolution that the hydrogen positions can be precisely determined. We use such data to refine our solution free ligand dynamic structures determined by NMR.
We demonstrate that structure determination by powder diffraction (SDPD) can be performed much more readily than is commonly believed, providing a new stream of conformational data for our chemistry design team.
Using the Conformetrix technology, we show how a series of drug molecules is likely to be mimicking the shape of a native peptide ligand. This work illustrates how scaffold-hopping from peptides to drugs can be readily achieved.
Here we detail how we measure ligand conformetrics using NMR and establish their relationship to the target-bound conformation. These breakthroughs lie at the heart of the productivity of our drug discovery engine.