Drugging Challenging Cancer Targets Using Fragment-Based Methods

There are many highly validated cancer targets that are difficult or impossible to drug due to the absence of suitable pockets that can bind small molecules. Fragment-based methods have been shown to be a useful approach for identifying ligands to proteins that were previously thought to be undruggable. In this review, I will give an overview of fragment-based ligand discovery and provide examples from our own work on how fragment-based methods were used to discover high affinity ligands for challenging cancer drug targets.