Protein-protein interactions (PPIs) play important roles in regulating cellular processes including enzyme catalysis, cell signalling and development, and protein homeostasis. For these reasons, targeting PPIs, directly or allosterically, provide compelling strategies for modulating protein function. However, it remains challenging to design and develop small molecules that bind with high affinity and specificity to PPI sites. The Src homology 2 (SH2) domain, found in over 110 human proteins, serve as a key mediator of PPIs facilitating recognition and binding of phosphorylated tyrosine residues in partner proteins . SH2 domaincontaining proteins are attractive therapeutic targets due to dysregulation in many diseases, including cancer . Significant efforts to target SH2 domains in the 1990s and early 2000s largely proved unsuccessful (phosphomimetics) chemistries and phosphate-masking capping prodrugs have offered alternative strategies, however, have largely remained niche and mostly target-dependent in scope .