Allosteric modulation

Allosteric modulators are an emerging class of orally available small molecule therapeutic agents that may offer a competitive advantage over classical drugs. This potential stems from their ability to offer greater selectivity and better modulatory control at disease mediating receptors. Most marketed drugs bind receptors where the body’s own natural molecular activators (i.e. endogenous ligands) bind, specifically to a key part of each receptor’s anatomy called the “active site”. In short, most drugs must out-compete endogenous ligands in order to bind to the active site.

Allosteric modulation chart

By contrast, allosteric modulators are non-competitive because they bind receptors at a different site and modify receptor function even if the endogenous ligand also is binding. Because of this, allosteric modulators are not limited to simply turning a receptor on or off, the way most drugs are. Instead, they act more like a dimmer switch, offering control over the intensity of activation or deactivation, while allowing the body to retain its natural control over initiating receptor activation.

Underlying the robust pipeline is our industry leading proprietary allosteric modulator discovery technology platform. Over the last 10 years, we have invested significant resources and time in building the infrastructure and developing the expertise for discovering and developing highly selective oral small molecule allosteric modulators.

Our platform allows industrial scale high throughput screening and can be adapted for a broad range of targets, including targets considered “undruggable” using conventional approaches.

Already we have succeeded in selectively targeting GPCRs, such as the glutamate receptors and the GLP-1 receptor with potent oral small molecules. More recently, our platform has shown success with new types of targets, such as receptor tyrosine kinases (RTKs), like TrkB, and other single-pass transmembrane receptors, such as the cytokine receptor TNFR1. Our technology platform can also be used effectively to target enzymes in a very selective manner, such as the epigenetic enzymes, kinases and bacterial enzymes. These targets span a broad range of therapeutic areas, including CNS, inflammation, metabolic and oncology indications.

In short, we are expanding the realm of druggable targets with our technologies for discovering oral small molecule allosteric modulators.