Biological and Medicinal Chemistry

From Inhibition to Degradation: Targeting the Anti-apoptotic Protein Myeloid Cell Leukemia 1(MCL1)


Here we show the development of heterobifunctional small molecules capable of selectively targeting MCL1 using a Proteolysis Targeting Chimera (PROTAC) methodology leading to successful degradation. We have confirmed the involvement of the E3 ligase CUL4A-DDB1 cereblon (CRBN) ubiquitination pathway, making these PROTACs a first step toward a new class of anti-apoptotic BCL-2 family protein degraders.


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