Potency assay, off target (cells):
Global quantitative proteomics screen was conducted in LCC2 cells after 36 h of treatment with BY13. Although WB analysis has confirmed that compound BY13 could significantly degrade SRC-3, diaPASEF-based quantitative proteomics analysis revealed only moderate degradation of SRC-3 (−log2FC = −0.25).
Probe Selectivity in
Cell:
Both ERα and CDK4 protein levels were profoundly downregulated by BY13.
BY13 containing pomalidomide moiety showed no appreciable off-target degradation activity against ubiquitously recognized CRBN substrates (e.g., CK1α and GSPT1). Other CRBN neo-substrates such as IKZF1, IKZF2, and IKZF3 were not detected in breast cancer cells before and after BY13 treatment.
