Proteome profiling of MOLM-13 cells treated with proposed CK1α degraders

Targeted Protein Degradation (TPD) encompasses two approaches that generate small molecules with similar proteasome-dependent mechanisms of action: Proteolysis-Targeting Chimeras (PROTACs) and Molecular Glues (MGs). Our goal is to develop novel MG approaches that exploit the E3 ubiquitin ligase Cereblon (CRBN) to degrade key oncogenic drivers in the leading causes of childhood cancer death: acute myeloid leukemia (AML). This project will identify new vulnerabilities and compounds that degrade hitherto undruggable transcription factors in high-risk acute leukemia (AL) and medulloblastoma (MB). Based on our preliminary data, we hypothesize that each of these compounds (SJ001010039, SJ001010040, SJ001010041, SJ001010047, SJ001010050) degrades CK1α in this cell line and may degrade other proteins. Our aims are to confirm that CK1α is degraded by treatment with each of these compounds and to identify any additional proteins that are targeted for degradation by these compounds.