Exploiting the long and short
More than 20 different subtypes of PDE4 enzymes are involved in the targeted degradation of cAMP. Between them, these enzymes co-ordinate a vast array of cellular responses and have long been considered as attractive targets for therapeutic intervention.
A major issue has been that the different subtypes of PDE4 enzymes, which cause different targeted effects, all have near-identical catalytic sites. Despite major efforts, successful development of inhibitors that are selective for the subtypes involved in disease, over those involved in the side effects has so far been elusive. By evaluating PDE4 enzyme structure and function in new ways, scientists at Mironid® have made breakthroughs that are set to bring forth a new era of PDE4 drug discovery.
Mironid’s approach involves the design of these precision tools (drug molecules) that target individual types of PDE4 family members rather than all enzymes within this large family. By doing this we can focus on regulating specific PDE4 family members to make sure we only modulate the cAMP signalling that is responsible for disease.
Our long-form specific Activator (LoAc®) programme has developed small molecules that selectively increase long-form PDE4 isoform activity, which in turn decreases cAMP signalling, whereas our short form versus Long form specific inhibitor programme (ShoLo®) has developed small molecules that selectively inhibit the short form of PDE4, leading to increased cAMP signalling.