Abstract

Starting Small and Staying Small: A Guiding Principle for Fragment Library Design and Fragment Optimization for Drug-like Properties

Vicki Nienaber, CSO, Zenobia Therapeutics, Inc.

“It can scarcely be denied that the supreme goal of all theory is to make the irreducible basic elements as simple and as few as possible without having to surrender the adequate representation of a single datum of experience,” later simplified to “Everything should be made as simple as possible but not one bit simpler.”        ---- Albert Einstein

This is a guiding principle in science and easily applied to the field of fragment-based lead discovery. Since its inception in the mid-1990 by Abbott laboratory scientists, it has grown into an accepted world-wide method of drug discovery. The number of metrics has grown, as have the number of approaches, and library molecular weights, sizes and shapes. At Zenobia Therapeutics and our products division, Zenobia Fragments, we have taken a step back and sought to distill FBLD down its basic scientific principles and guidelines.  We will discuss our library design process and criteria, screening strategy including number of compounds screened and approach to optimization where a specific, bioavailable and efficacious LRRK2 inhibitor was identi