β-catenin-BCL9 interaction is an important new target in cancer therapy. We aim to develop high affinity (Kd < 100 nM) small molecule inhibitors of the β-catenin-BCL9 interaction using a fragment-based method. Fragment-based screening is often used in drug discovery where low molecular weight (< 300 Da) fragments are screened for protein binding. The fragment hits are then optimized to small molecule inhibitors via stepwise growing or linking the fragments together.