The development of 53BP1 inhibitors using REFiL– an efficient workflow for early stage hit to lead optimisation in FBDD

Breast cancer is a commonly diagnosed form of cancer. A person is 6-times more likely to develop breast cancer if they have inherited mutations to the BRCA-1 gene. One potential means of preventing this is by inhibiting a protein called 53BP1. This work details the synthesis and testing of over 1000 potential drug-like compounds against 53BP1. It also demonstrates one of the first applications of a novel workflow hoped to expedite drug discovery called REFiL – the Rapid Elaboration of Fragments into Leads. In under 3 years, 7 promising leads were identified against this potential new anti-cancer target.