PLATFORM

Studies have demonstrated that drug sensitivity information at the level of the proteome is not available at the level of the corresponding DNA or mRNA. This underscores the benefit of searching for drug targets at the level of their functional protein products. Our idTRAX (Identification of Drug TaRgets and Anti-targets by Cellular and Molecular Cross-referencing) technology improves the process further by querying drug targets directly at the level of their biochemical function.  By screening compounds with known biochemical activities on cellular models of disease, then relating the resultant cellular phenotypes to the compounds’ biochemical activities, drug targets can be identified in a direct and rapid manner. This strategy identifies targets that are pharmacologically responsive, readily druggable, and are not easily overcome by the robustness of signaling networks, because only targets that effectively induce a phenotype upon pharmacological engagement are identified by the process. As an example, we previously used this approach to identify S6K1 as a drug target for axon regeneration. S6K1 had evaded years of extensive study in the field, including numerous genomic, transcriptomic, and proteomic analyses. Applications to other disease models, including cancer and viral infection, have been equally promising. The approach is theoretically applicable to any family of drug targets.

 

We are developing the first iteration of the platform around kinases for a number of important reasons:

 

  • kinases are involved in mediating most cellular processes, and can, therefore, serve as drug targets in a wide range of therapeutic applications
     

  • kinases are readily druggable
     

  • the existence of a large number of kinase inhibitors allows us to develop our chemical probe set without a resource and time-consuming chemical synthesis program
     

  • reliable kinase assays available commercially or through our partners make profiling kinase activities relatively easy
     

  • the polypharmacology between kinases can be used to therapeutic advantage
     

  • we have more than 10 years of experience with screening small-molecule kinase inhibitors in phenotypic assays.

 

The successful deployment of our platform requires two critical components: a specially formulated chemical probe set and a companion target deconvolution algorithm .