Abstract

Neuropilin-1 (NRP1) is a receptor for vascular endothelial growth factor A165 (VEGF-A) and the neuronal guidance molecule semaphorin 3A (SEMA3A), which plays a key role in vascular and neuronal development. Molecules which antagonise the interaction of NRP -1 with its protein ligands may be useful in a number of therapeutic settings, in particular for the treatment of certain types of cancer.

In collaboration with our client, Ark Therapeutics, and with scientists at University College London, we have designed the first small-molecule inhibitors of this protein-protein interaction and have shown that they display the expected pharmacological profile.  This talk will describe our rational approach to the identification of the binding mode of the natural ligands, and how we used this information to drive the de novo design of antagonists that provide a chemical template from which clinically useful therapeutic agents can be evolved.