Despite significant progress over the past few decades in developing small molecule therapeutics against drug targets with clearly defined binding sites, the majority of potential targets in human disease do not fit current models of drug discovery. Well-known oncogenic targets such as MYC and ARv7 that function as transcriptional drivers or through other protein-protein interactions are often poorly suited to traditional high-throughput screening or rational design. The targets are frequently disordered when isolated from binding partners or physiological complexes, generally lack obvious binding pockets, and may act through complex signaling pathways. Despite a wealth of data implicating these oncogenes in some of the deadliest forms of cancer, no approved therapeutics exist. Thus, there is a critical need for new approaches to discover drug candidates against these targets.