Addex Therapeutics - Allosteric Modulators Technology

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. 

Addex is the first company that has developed high-throughput industrial discovery tools for allosteric modulators. Addex has developed proprietary real time kinetic and proximal detection systems that permit the identification of allosteric modulators which modify the molecular response of their target. 

The company’s approach to leveraging and maintaining its competitive advantage is to keep certain aspects of its platform technology as trade secrets while patenting others. 

Proprietary screening assays developed at Addex include ProxyLite, Phoenyx, IntraSwitch, BBBA and AddeLite. These assays are used for screening G protein-coupled receptors (GPCR) and non-GPCR drug targets and are necessary to facilitate medicinal chemistry for lead optimization. 

ProxyLite?assay for GPCRs is an assay applicable to all GPCRs, family A through C, Gi-, Gs- or Gq-coupled. Signal measurement is dynamic and real-time, allowing kinetic analyses of activation and change induced by allosteric modulators. The overall result is a truer readout of receptor activation, allowing a better detection of allosteric modulators of GPCRs. 

Phoenyx is part of a series of HTS-compatible biosensors allowing measurement of intracellular cascades turned on by receptor activation, offering multiple possibilities to confirm activity of allosteric modulators and probing biased signaling.

IntraSwitch assay allows real-time assessment of receptor change of conformation when getting activated. This represents a powerful way to ‘visualise’ effects of allosteric modulators directly on receptors of interest.

BBBA assay is a non-radioactive binding assay developed specifically for allosteric modulator programs. It provides a rich pharmacological information to expand our understanding of  how compounds bind to the allosteric pocket.

AddeLite?assay for non-GPCRs is an assay applicable to all single-pass transmembrane proteins. It offers a unique way of measuring dynamically the activation of receptors of interest which have historically been difficult to address with small molecules. AddeLite?assay is highly appropriate for high-throughput screening, offering an exquisite sensitivity to detect allosteric modulators.

The implications are: 

1. Allosteric modulators are not in the same structural space where pharma chemists are used to working. As a result, Addex has built not only a unique library but also multidisciplinary know-how pertaining to different kinds of chemical structures. 

2. Intellectual property within the allosteric structural space is relatively unexploited, making discovery and optimization less encumbered by the need to avoid pre-existing patent families, which can often be a challenge for traditional small molecule chemistry efforts.