Fragment-based screening: A new paradigm for ligand and target discovery.

Abstract

Significant advances in fragment-based screening, including the emergence of Fully Functionalised Fragments (FFFs) and innovations in Covalent Fragment screening are providing a new paradigm for ligand and target discovery. FFFs offer some key distinct advantages over other screening modalities such as small molecules and genetic screens, including 1) An ability to access diverse chemical space employing a relatively small compound set 2) Ease of screen optimisation given there is no requirement for genetic manipulation and 3) Built-in proteomics tools to facilitate rapid target deconvolution directly in cells. Covalent fragments enable exploration of novel druggable nodes through irreversible fragment-cysteine interactions, complementing their fully functionalized counterparts. Both FFFs and Covalent fragments present the phenotypic screening community with an additional and complementary approach for disease centric target identification.