Smart Allostery™ is being leveraged across entire target classes to speed pipeline development and value creation. To date, our platform has reproducibly drugged sought-after targets across three protein classes including protein classes including kinases, transcription factors and E3 ligases.Learn more ABOUT OUR PIPELINE
Elucidating natural hotspot targets
Uncovering natural hotspots is a daunting challenge due to the variety of mechanisms that nature has developed to control the cell. Unlike active sites, natural hotspots are often hidden from sight and require a deep understanding of structure-function to unveil. The Smart Allostery™ platform takes a systems-wide view to uncover protein pockets with previously unknown regulatory relationships.
Approximately 1,500 proteins have been identified containing natural hotspots that control protein function.
HotSpot Therapeutics’ Smart Allostery™ platform is the first technology platform designed to systematically identify natural hotspots and enable the design of potent, selective allosteric modulators.
We integrate insights from biology, computational sciences, chemistry and biophysics to systematically identify and drug regulatory natural hotspots.
Smart Allostery™ has three key elements – SpotFinder™ to Uncover, HotSpot Toolkit to Capture and Tailored Chemistry to Drug – offering unique dry lab-wet lab integration under one roof.
SpotFinder™ to Uncover
A suite of proprietary ML/AI algorithms are trained to identify the fingerprints of natural hotspots in proteins. HotSpot’s computational platform enables full annotation of target class-derived pocketomes with respect to structure-function and site druggability. Clustering pockets on the basis of evolutionary origin generates deep insights across related proteins, while providing an entry point to selective small molecules.
HotSpot Toolkit to Capture
A toolkit of pharmacology and in silico assays stabilize specific protein-pocket conformations to display the often transient regulatory sites in an open and accessible state. High-affinity regulatory peptides can then be used as molecular screening tools to accelerate lead identification.
Tailored Chemistry to Drug
Custom chemical libraries are produced based on the 3D pharmacological footprint of natural hotspots. Using an in-house DNA-encoded library (DEL) platform, HotSpot Therapeutics has produced over 800 million compounds, establishing the industry’s most diverse hotspot- targeted chemical collection. Hit mining using ML/AI and structure-based algorithms accelerates both hit finding and chemical diversification.