Silent Allosteric Modulators

DTect-All™ enables identification of any modulator interacting with the GPCR 7TMD. Using a secondary functional screening, these modulators are further characterized as Positive (PAMs), Negative (NAMs) or Silent (SAMs) Allosteric Modulators. This last category, representing 7TMD binders that exert no activity in a specific functional assay, is systematically identified in our screening campaigns.

SAMs represent a useful source of molecules for the discovery of novel families of modulators. Indeed, slight chemical modifications of these SAMs can switch them to functionally active PAMs or NAMs. This approach constituting an innovative way to make accessible a broader chemical space for allosteric modulator identification was already validated with family II and III GPCRs

Moreover, as it is well known that allosteric modulator activity is highly dependant of conditions of the functional assay, SAMs can also be subjected to a larger functional characterization to unveil an activity not initially detected.