Our Approach

Fragment Library

Since Zenobia is targeting the CNS, our fragment library has been designed with a set of criteria that is different from other commercial libraries.  These criteria ensure that compounds identified in screens are appropriate for optimization into a clinical candidate with chemical properties consistent with marketed CNS therapeutics.  This library is also appropriate for other indications and provides the opportunity for additional rounds of optimization or a lower overall molecular weight for the resulting clinical candidate.

Fragment Screening

Our years of experience with FBLD allow us to choose the right tool for each program.  We have routine access to thermal melt shift, high-concentration biochemical screening, NMR and nanocalorimetry screening methods.  For our active drug discovery programs, we have used Tm shift, nanocalorimetry and biochemical assay. All methods filter into crystallographic analysis as a secondary screen.  At the end of the screening process, we have a diverse set of hits with potencies and crystal structures.  Compounds are chosen for synthetic optimization based upon these data.

Fragment to lead

Fragments are optimized in an iterative structure-guided manner.  Ligand efficiency and chemical properties are monitored at all stages of the design process to ensure the lead compounds is appropriate for a CNS therapeutic agent.