Exploring new fragments of chemical space

I’ve spent the last few years of my life making medicines, and I’d highly recommend it. UK pharma is, broadly, a great place to be and many of my past and present colleagues report making a difference to patients’ lives as one of their main driving forces.

But the process isn’t simple at all. Med chemists start small, sometimes with sub-300g per mol molecules called fragments. Fragments are too small to definitively exhibit the physicochemical properties of the drug substance they will grow into. This means they can be rapidly screened against a single objective – effectiveness against the protein target. (In the same vein, they can also be tested for their selectivity – the lack of unwanted effects on other proteins in the body.)

The experimental design simplicity of single-objective optimisation makes it possible to screen a huge variety of fragments, in terms of shape, flexibility, electronic features, hydrogen bonding capabilities and any other molecular design parameters we can choose. This diversity is continually increasing as specialist vendors build catalogues of fragments that enhance coverage into previously unexplored chemical space.