The scientists of TREVENTIS™ have been working in central nervous system (CNS) drug design for over a decade. We have developed a unique in silico model of protein misfolding disorders that can be used, in the absence of a crystal structure, to perform virtual screening campaigns for anti-misfolding compound hits and to effectively perform hit-to-lead optimization in our synthetic programs.
This proprietary, patent-pending model, dubbed Common Conformational Morphology (CCM), was developed using homology modeling and molecular mechanics/dynamics of intrinsically disordered proteins (amyloid or amyloid-like).
- available crystal structures of amyloid proteins outside the CNS
- extant structural information for CNS amyloid proteins such as Aβ and tau
- lists of (non-drug) literature compounds that inhibit more than one amyloid protein
We pinpointed the likely binding sites of anti-misfolding compounds for their respective amyloid proteins. We have used this CCM platform to produce models of protein misfolding against many intrinsically disordered proteins. As part of the CCM approach, TREVENTIS™ scientists have also created and optimized experimental systems (in vitro and in vivo) to interrogate the earliest phases of oligomerization and aggregation.
In short: TREVENTIS™ CCM is a mechanism-based, rational drug design approach to protein misfolding therapeutics that can be applied in the CNS and beyond.