Tom presents work on small molecule inhibitors of Hhat in Brighton

Tom gave a talk and poster presentation on the Tate groups’ research into small molecule inhibitors of the enzyme Hedgehog acyltransferase (Hhat)

The work was presented in Brighton this month at the Biochemical Society’s meeting entitled 'Acylation of intracellular and secreted proteins: mechanisms and functional outcomes.’ Tom was also awarded a prize for his accompanying poster.

Hhat is a multipass transmembrane protein and its activity is required for Hedgehog signalling which promotes growth in certain cancers, thus making Hhat a potential therapeutic target. The Tate group has developed synthetic routes to the ‘RUSKI’ class of small molecule inhibitors of Hhat, along with means to modulate their conformational properties. These inhibitors have been analysed using a chemical biology approach to identify an on-target Hhat inhibitor, RUSKI-201. The group has also designed new biochemical assays for Hhat activity, using click chemistry-armed ELISA or microfluidic mobility shift formats. These tools will support further development of Hhat inhibitors in future.