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.

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, 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. Since founding in 2002, 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 gonadotrophin FSH, muscarinic M4 receptors from class A, GLP-1 receptor from class B, and metabotropic glutamate and GABA receptors from class C. More recently, our platform has also demonstrated its power by successfully identifying small molecule allosteric modulators of new types of targets, such as TrkB the receptor for brain-derived neurotrophic factor. Targets in our pipeline 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.