The MET kinase, along with its oncogenic alterations, is a clinically validated target for the development of anticancer medicines. The emergence of resistance to first-generation inhibitors necessitates the development of new compounds able to inhibit both wild-type enzyme and resistant mutants. In this presentation, we will describe our hit-finding efforts aimed at discovering allosteric MET inhibitors and the subsequent optimization of one class of allosteric type III sulfonamide inhibitors. Starting from a DNA-encoded library technology (DELT) hit, and guided by ligand-bound x-ray co-crystal structures, this process led to highly potent macrocyclic compounds with promising molecular properties. These compounds could serve as starting points for the design of next-generation MET inhibitors.