Membrane and Raft Intervention

Membrane Modulators

The lipid raft provides a stabilized multicomponent structure in which proteins are brought into close proximity to trigger an event. JADO targets the raft for pharmaceutical intervention by interfering with protein activation at the level of the membrane rather than at the active receptor sites. This is a form of allosteric modulation, an emerging tool for drug discovery and development.

Through its research, JADO has developed an understanding of the chemistry required to target specific membrane domains and has confirmed the activity of multiple small molecules in various disease models.

Thus although many biological processes take place in the same membrane, it is possible to specifically target a selected event without triggering side-effects caused by interaction with other essential membrane processes.

Membrane Modulator Library

JADO's unique compound library consists of over 1000 chemical structures containing a high proportion of new chemical entities (NCEs).

Rapid harvesting of information from different disease models combined with in-silico modeling techniques has provided JADO with the basis for rational design of membrane and raft-targeted compounds.

JADO has demonstrated that structures generated in this way are pharmaceutically active in cellular models of allergy, influenza, tuberculosis and Alzheimer’s disease.

Raftophiles

Raftophiles are efficient molecular delivery vehicles that serve to anchor pharmaceutically active compounds to the cell membrane in close proximity to the relevant protein targets. They have high affinity for rafts and can be attached via a linker molecule to a drug specific for any raft-located protein.

The raftophile positions the drug at the site of action in the cell membrane by co-localizing with the target raft protein. Through this action, an apparent increase in potency of 100-fold to 1000-fold can be achieved.

Raftophiles also facilitate cell penetration of polar drugs that would otherwise not cross the membrane, thereby make an apparently inert drug highly active.

JADO demonstrated the utility of this concept in Alzheimer’s disease (Science 320, 2008).