The oncogene MYC drives many cancers and is an outstanding therapeutic target. MYC is an intrinsically disordered protein, and therefore, targeting MYC remains a challenge. Here, we developed a proteolysis targeting chimera (PROTAC) degrading MYC: MDEG-541. The inhibitor is based on the MYC-MAX dimerization inhibitor 10058-F4 and Thalidomide. Mode of action depends on the proteasome and cereblon. MDEG-541 shows single digit mM activity in most sensitive colon and pancreatic cancer cell lines as well as gastrointestinal tumor organoids.