Science - HotSpot Therapeutics

Unlike conventional small molecule approaches to drug discovery, which focus on targeting active sites to catalyze specific molecular processes, our allosteric drug discovery process goes beyond the traditional active site.

This allows us to focus on the estimated 85% of the roughly 20,000 proteins in the human body that are considered undruggable by traditional active site approaches.

Allosteric drug discovery relies on control mechanisms that are distinct from an active site, which nonetheless exert functional influence over protein activity.

At the heart of these regulatory regions are privileged allosteric sites called natural hotspots that offer attractive biological real estate for drug discovery.

Hotspot medicines offer

Broad applicability
Allosteric pockets may exist on most proteins and are not limited to those with substrate turnover sites only, enabling the targeting of previously inaccessible biological pathways relevant to serious diseases.

Enhanced pharmacology
Allosteric therapeutics can modulate functions such as protein conformation, scaffolding and cellular translocation, resulting in broader, tunable pharmacology including protein inhibition, activation, degradation or stabilization.

Increased selectivity and specificity
The structures of allosteric pockets tend to differ significantly within a specific protein class, enhancing the ability to design drugs with a high degree of selectivity and minimizing the potential for off-target liabilities.

Improved drug-like properties
The balanced topography of allosteric pockets may simplify the engineering of drugs targeting these allosteric sites, leading to characteristics that facilitate improved patient convenience, such as reduced pill burden and dosing frequency.

Hotspots in action

Through natural hotspots, evolution has devised a means to selectively correct for chemical imbalances and dysregulation to restore health and proper functioning, both in normal biological activity and in disease.

Traditional Active Site Discovery

Conventional Allostery
Natural Hotspots

Smart Allostery™ Platform

Our technology platform, Smart Allostery™, is designed to systematically identify and drug natural hotspots across the proteome, including protein classes largely considered undruggable.