TMT analysis of MOLM-13 cells treated with SJ001007095

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 compound SJ001007095 targets AML cells independent of GSPT1 degradation. Our aims are to understand the mechanism by which compound SJ001007095 targets AML cells using TMT proteomic approach and identify proteins targeted by the compound SJ001007095 leading to their degradation and consequently AML cell death.