Technology
Fragment-based lead discovery (FBLD) is
a method that was developed and first implemented at Abbott
laboratories during the mid-1990s. Zenobia founders Vicki Nienaber and
Robert Meadows have been actively involved in the field since its
inception. Early approaches included NMR spectroscopy and
x-ray crystallography which have worked together successfully to produce
multiple clinical candidates. Newer methods include surface plasmon
resonance (SPR) which has been used interchangeably with NMR as a
pre-screen for fragment binding. Additional methods used by Zenobia are
thermal melt (Tm) shift analysis and nanocalorimetry which is a method
developed by our collaborators at Palo Alto Research Center.
Zenobia uses FBLD as a core technology for their internal drug discovery program and as a discovery service to outside organizations.
Zenobia uses FBLD as a core technology for their internal drug discovery program and as a discovery service to outside organizations.
When fragment-based lead discovery was first introduced in the mid-1990,
many were skeptical that a small weakly binding fragment could be optimized into a potent inhibitor and eventually a clinical candidate. However, the concept of starting with a small fragment and staying small while closely monitoring ligand efficiency and other chemical properties has yielded more than 15 clinical candidates and its first marketed product, Vemurafenib.
As the importance of proper molecular weight and other chemical properties has become more appreciated for ultimate success in the clinic, the method continues to gain in popularity.
As the importance of proper molecular weight and other chemical properties has become more appreciated for ultimate success in the clinic, the method continues to gain in popularity.
