OUR SCIENCE
β-Propellers
Mediators of protein complex assembly and their biological function, they are ubiquitous within human biology. Mapping their interactions and exploiting their therapeutic potential requires a rigorous scientific platform.
Context is Critical
It will unlock an expanse of new drug targets.
Proteins do not function in isolation. Disease biology does not occur in isolation.
Drug developers largely execute drug discovery on the protein target in isolation, inhibiting the protein to thwart its specific function. This focus on a singular protein significantly limits the universe of targets – most proteins do not play a functional role or have proven to be undruggable.
When β-propellers are misregulated, they become part of processes that drive disease. Because β-propellers can be drugged within a specific biological complex of interest, they have the potential to modulate the targeted pathway with more specificity than conventional protein-targeting approaches.
Early work in the field has shown that β-propellers are druggable. Mining and credibly interrogating them as a class presents an enormous opportunity to expand the universe of tractable protein targets.
The emerging class of β-propeller proteins has not been credibly evaluated.
Until now.
Evidence now demonstrates the therapeutic value of targeting β-propellers.
There are more than 600 known β-propeller containing proteins. These stable, adaptable proteins mediate precise, contextual protein interactions with proteins, nucleic acids, and other biomolecules. Critically, these complexes drive the pathogenesis of many diseases, including cancer, neurodegeneration, metabolic disease, and inflammation.
Focused Insights
The set of skills and technologies needed to successfully take on β-propellers are now available. Our platform brings them together.
Using advanced computational approaches and protein interaction mapping as our foundation, we are building an atlas of β-propellers and the protein complexes they control - enabling us to make well-informed decisions about therapeutically relevant targets.
This combination of tools provides us with the ability to identify and validate β-propeller-driven disease progression and:
Prioritize targets for drug discovery efforts
Elucidate the function of targets in disease-specific contexts
Discover and develop highly selective therapies against these targets
Inform on patient populations most likely to benefit from these therapies
Why β-propellers?
β-propellers have unique properties not shared by other proteins, which make them an abundant source of promising targets.
Accessing the Intractable
Because they are ubiquitous in human biology, they represent a completely novel avenue to broadly target the protein complexes that were previously inaccessible.
Specificity
β-propellers interact with other proteins in a context-specific manner, acting as a hub within disease-driving protein complexes. Once a target is linked to a complex of interest – we can target it with a high degree of specificity, without shutting down a protein’s function systemically.
Highly Druggable
β-propellers have consistent folds, presenting binding pockets accessible for traditional small molecule targeting. Once a protein target is identified, it is readily druggable.
Forward Momentum
We are developing an atlas of β-propeller protein interactions. Each insight into how they drive disease feeds our next target of interest.
Patterns and themes in biology, structure, and function are emerging, unveiling the rules to pharmacologically target them. This compounding effect is accelerating future drug discovery and development programs and enabling rapid identification of novel targets and therapies.
Our broad efforts are confirming this. We have identified a portfolio of druggable propeller targets and are building an emerging pipeline of therapies
