With the encouraging results presented by the heterotrivalent PROTAC series, we wanted to further investigate the chemical space and synthesise a compound which would more closely resemble SIM1, aiming to retain the avidity and BET bivalency it displays, 11 but now adding the ability to recruit two E3 ligases instead of just one. The so-called "heterotetravalent PROTAC" would be a combination of heterotrivalent PROTAC AB3063 ( ) and BET-bivalent, trivalent PROTAC SIM1. We therefore decided to functionalise from the methyl group of the central quaternary carbon present in the linker of SIM1 as a potential vector to recruit CRBN by adding another linker tethered to thalidomide. We chose to synthesise a linker which would again allow for: simple amide coupling to the VH032; future SNAr to a fluorothalidomide derivative; and diesterification to JQ1 (Scheme 5). The synthesis follows a similar route to the one used for heterotrivalent PROTACs (Schemes 2 & 3).