Our capabilities

Addex is the first company that has developed patented 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 outcome of the GLP-1 receptor screening and development of assays leading to the discovery of TNFR1 NAM and IL-1R1 NAM illustrate the power of the unique and proprietary technologies discovered and used at Addex.

Screening assays

Addex is the first company that has developed patented 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 outcome of the GLP-1 receptor screening and development of assays leading to the discovery of TNFR1 NAM and IL-1R1 NAM illustrate the power of the unique and proprietary technologies discovered and used at Addex.

Many aspects of these technologies have been patented in order to protect and document our leadership position in allosteric modulator drug discovery. 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 PhoenyxTM, ProxyLiteTM, APRATM, ADX-tags 1TM, ADX-tags 2TM. These assays are used for screening GPCR and non-GPCR drug targets and are necessary to facilitate medicinal chemistry for lead optimization.

ProxyLiteTM assay for GPCRs is a proprietary assay applicable to all GPCRs, family A through C, Gi-, Gs- or Gq-coupled. On the contrary of conventional assays that measure downstream effects such as changes in secondary messengers like calcium or cAMP, ProxyLiteTM measures receptor activation directly at the receptor. Signal measurement is dynamic and real-time, allowing kinetic analyses of activation and change induced by allosteric modulators. Compared to conventional assays, ProxyLiteTM yields superior results in screening, with less false positives and less false negatives. Moreover, it offers a significantly higher rate of confirmation of primary hits, with 3 out of 4 hits identified confirmed, compared to 1-3 out of 10 hits identified using conventional assays. The overall result is a truer readout of receptor activation, allowing a better detection of allosteric modulators of GPCRs.

AddeLiteTM assay for non-GPCRs is a proprietary 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. AddeLiteTM assay is highly appropriate for high-throughput screening, offering an exquisite sensitivity to detect allosteric modulators.

Chemistry

Since inception in 2002, Addex has assembled a unique biased library of molecules with allosteric characteristics. The library has been assembled from commercial and other non-pharmaceutical sources, with some parts of the library acquired under exclusive agreements. At the end of 2009, Addex chemists had assembled over 70,000 compounds. The Addex selection process includes filtering for basic drug-like characteristics and development potential. An additional level of filtering involves the application of proprietary algorithms focused on identifying characteristics of allosteric molecules. A multivariable analysis of the Addex library, depicted here, shows that while its molecules share the physicochemical properties of marketed drugs they are structurally differentiated.

The implications are:

  • 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.
  • 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.