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  • About Lipid RAFTs
  • RAFT Intervention

Technology

RAFT Intervention

JADO has developed novel assays to model RAFTs and is utilizing advanced chemistry to create specific RAFT targeted molecules. These molecules are specific for the disease event, so discriminate between pathogenic and vital activities of the protein.

DISRAFTERS® - Modulators of Pathogenic RAFTs

DISRAFTERS® are small molecule inhibitors of RAFTs involved in different disease processes. DISRAFTERS® are able to modulate intermolecular interactions integrating RAFT lipids and proteins and thereby inhibit the formation of RAFTs in key pathogenic events. This innovative mode-of- action yields many novel compound scaffolds for drug development.

As each RAFT has a specific characteristic composition, DISRAFTERS® will be tuned by design to home in on this attribute and target distinct disease specific RAFTs.

Thus although many RAFT based processes are taking place in the same membrane, it is possible to specifically target and inhibit a selected event without side-effects or toxicity resulting from promiscuous interaction in other RAFTs.

RAFTOPHILES®

RAFTOPHILES® are efficient molecular delivery vehicles. They are small anchoring molecules with a high affinity for RAFTs (so-called raftophilicity). These moieties are attached via a linker to a drug specific for a RAFT protein. The RAFTOPHILE® can position the drug at its cell membrane site of action by taking advantage of co-localization with the target RAFT protein. In this way an apparent increase in potency of 100-1000 can be achieved.

RAFTOPHILES® can also facilitate cell penetration of polar drugs, which would otherwise not cross the membrane and thereby make an apparently inert drug highly active.

Compound Libraries

JADO's unique libraries consist of over 500 chemical structures containing more than 50 novel compound scaffolds designed to target specific RAFTs. JADO has developed proprietary libraries of DISRAFTER® and RAFTOPHILE® scaffolds using its unique expertise in RAFT chemistry and rational compound design.

Rapid harvesting of information from different disease models screened with DISRAFTER® libraries, combined with information on mechanism will allow JADO to map chemical spaces for RAFT intervention in different diseases.

The resulting structure data will allow predictive design of highly specific and efficient novel pharmaceuticals. Through its design and testing programs, JADO has accumulated Structure Activity Relationships (SAR) for DISRAFTERS® specific for influenza replication and immunogenic signaling. This is the only database worldwide informing on the rational design of membrane targeted pharmaceuticals.

RAFT Assays

JADO has at its disposal a number of specific disease model and cell biological assays for screening and optimization of DISRAFTER and RAFTOPHILE drug candidates:

•   Influenza virus replication, virus budding and virucidal activity
•   HIV replication, virus budding, and virucidal activity
•   SV40 virus uptake - caveolar dependent viral infection
•   Bacterial invasion - Mycobacterium infection (tuberculosis)
•   Immunogenic signalling (asthma and allergy)
•   Cholera toxin uptake - RAFT endocytosis
•   Beta-secretase activity (Alzheimer disease)
•   Apoptosis
•   Cell division

New assays are constantly being created.

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