The design of effective inhibitors of protein-protein interactions (PPIs) for therapeutic use has been a notoriously arduous and challenging task, making PPIs a largely untapped target space for new therapeutics. The molecular surface area involved in PPI is large enough to make inhibitor design difficult. However, covalent inhibitors have been explored to inhibit PPI. A recent example of a covalent PPI inhibitor is the (arylaminoalkyl)oxabicycloheptadienedicarboxylate COH000. COH000 reacts with a Cys residue located in an allosteric site of SUMO E1, stabilizing the enzyme in an inactive state. Other examples of PPI inhibitors include oridonin, an α-methylenepoxykaurenone small molecule inhibitor of NLRP3/NEK7 288 , and TED-347, a chloroketone small molecule inhibitor of TEAD/Yap 289 useful in the treatment of breast cancer and glioblastoma, respectively. Arylsulfonyl fluoride and aryl fluorosulfate warhead-containing small molecule covalent inhibitors of XIAP/BIR3