ProFACT News

 

Small molecule inhibitors of Phosphodiesterases and Kinases have proven successful in the clinic driving demand for methods to assess drug promiscuity and non-specific toxicity. While such methods are essential to the discovery process, two critical deficiencies remain: 1) proteomic analyses for broadly relating and characterizing the kinetics of enzyme variants responsible for the disease phenotype, and 2) proteomic analyses to assess in vitro drug responsiveness based on enzyme kinetics from heterogeneous mixtures such as from cell lines and tissue homogenates.

 

In this webinar, ProFACT describes advances in its proprietary functional proteomics platform – SeraFILE™, and related Conformerics™ prospecting strategies, for these purposes. We first will describe how we apply SeraFILE™, a novel proteomic separations and compartmentalization platform, to derive signature profiles of Phosphosdiesterase activity from different biological sources. Such profiles provide new and characteristic kinetic data which can be compared sample to sample, disease to non-disease, and tissue type to tissue type. Thus for biomarker discovery, these signature profiles help define a target set of observable differences in kinetic response to various in vitro stimuli of the active site – the variants, from those samples. The stimuli can come from drug candidates or competing substrates, and the variants potentially span the continuum of enzymatic sub-states generated by natural transient features and regulatory factors, post-translational modifications, amino-acid sequence (families, mutations), or splice variants.

 

We will also describe new methods for Kinase enrichment and how SeraFILE™ can be adapted to functional profiling of kinase activities and inhibitor selectivities. New strategies to prospect, enrich, and potentially identify the most responsive phosphodiesterases and kinases to a challenging inhibitor will be discussed.