Early Stage Drug Discovery
Identifying small molecules able to revolutionize drug discovery.
The PPI-FIT technology allows the exploration of unique pharmacological targets represented by protein folding intermediates. This places Sibylla Biotech in the exclusive position of identifying hit/lead compounds with a mechanism of action never explored so far.
In this direction, we have developed a virtual screening workflow to identify small molecules potentially able to bind the explored intermediate with high affinity. Depending on the project, hit identification is carried out using commercial chemical libraries (clinical/approved drugs, natural compounds, fragments, focused-libraries, diverse libraries etc) as well as client’s (or customer’s) proprietary compounds.
Virtual hits are carefully evaluated and selected also based on the physicochemical properties to ensure they have good developability profiles to streamline the hit-to-lead optimization. Once validated hits have been collected, focused libraries are generated and tested to build up structure-activity relationships and predict ADME properties to ensure further progress of the most promising “true hit series”
Witnessing the Birth of a New Generation of Pharmacological Degraders for Undruggable Targets.
Targeted protein degradation is an emerging concept in the drug discovery field. PPI-FIT introduces a completely new paradigm by which pharmacological degraders are designed. By acting on intermediate conformers appearing along the folding pathways, the technology generates molecules that directly promote the removal of the target protein without the need for heterobifunctional moieties.
Folding intermediates are protein conformers presenting distinct pockets as compared to their native counterparts. PPI-FIT exploits such a unique property to open up new opportunities for selectively targeting undruggable proteins. Our ongoing experience with the technology is driving the way we analyze PPI-FIT molecules. Indeed, since the method acts on folding intermediates, our experimental investigation is tailored to detect pharmacological effects at the level of nascent protein chains. Next, we employ context-dependent, disease-relevant assays to evaluate the therapeutic potentials of each individual hit.
At the end of the process, the selected molecules enter into a hit-to-lead workflow to provide compounds suitable for in vivo tests.
Sibylla plays a role in the B2B drug discovery market, targeting Pharma industries’ need of out-sourcing discovery and preclinical studies.
As a service-based activity, we may work in collaboration with Pharmaceutical and Biotech companies.
We can apply the PPI-FIT protocol to targets of their interest, delivering the identification of new druggable pockets identified on the folding intermediate state and eventually virtual hits or identified hits on cell-based assays.