BET proteins are involved in mul3ple diseases associated with the misregula3on of immune response genes. Through the parent grant we are characterizing the ET domain for its poten3al as a drug target and iden3fying the origin of selec3vity across homologous ET domains. Within this supplement we take a further step and propose the design and characteriza3on of pep3de macrocycles as poten3al drugs using an array of computa3onal chemistry tools, which we will later characterize with our experimental collaborators.