Crystal Structure of ROCK 1 kinase bound to fasudil / Structure of fasudil

The first example of fragment-based identification of an active molecule was described in 1996. The idea was to assay small molecules (molecular weight below 350) using NMR or X-ray techniques at high concentration against the protein of interest to identify active fragments. Two fragments showing affinity at different location of the site are then chemically connected to obtain a final molecule with high affinity to the receptor.

Since then, many example have shown that fragment-based drug discovery is a powerful tool to help medicinal chemists attain optimisation of their molecules. However, no new active compound discovered only with this technique is currently described. There is a need for second and third generation fragment compounds to master the hardest part of the technique - the connectivity between the fragments.