PROTAC BCR-ABL1 ligand 1, also known as compound GMB-475, is a PROTAC ligand that allosterically targets the BCR-ABL1 protein. It recruits the E3 ligase Von Hippel-Lindau, leading to the ubiquitination and subsequent degradation of BCR-ABL1. It demonstrates cell proliferation inhibition with IC50 values ranging from 0.37 μM to 1.98 μM for different BCR-ABL1 cell types and induces the degradation of BCR-ABL1 and c-ABL1, inhibiting downstream signaling via the STAT5 pathway in a dose- and time-dependent manner.
- Targets the BCR-ABL1 protein allosterically
- Recruits the E3 ligase Von Hippel-Lindau
- Leads to ubiquitination and degradation of BCR-ABL1
- Induces degradation of BCR-ABL1 and c-ABL1
- Inhibits downstream signaling via the STAT5 pathway