Merging enzyme-response chemistry with PROTAC technologies, the overexpression of the NAD(P)H quinone dehydrogenase 1 (NQO1) enzyme in cancer cells has inspired the design of trimethyl-locked quinone cages attached to Hyp of VHL-recruiting PROTACs, envisioned to release the active PROTAC upon quinone reduction by NQO1. Here, VHL is linked to cancer.