Potency assay, off target (cells):
Degradation selectivity of AK-1690 was evaluated on a global level by proteomics. Human PBMCs were treated with AK-1690 at a high concentration (5 μM) for a long duration (18 h).
Probe Selectivity in
Cell:
With 18 h treatment at 5 μM, AK-1690 reduced the levels of only four proteins by ≥50% out of >6,000 proteins detected. Specifically, the STAT6 protein level was decreased by 79%, whereas the levels of EPB41L1 (erythrocyte membrane protein band 4.1), KRT1 (Keratin 1), and AKR7A3 (aldo-keto reductase family 7 member A3) were reduced by 60%, 59%, and 51%, respectively.
Levels of other members of STAT family proteins (STAT1, STAT2, STAT3, STAT4, STAT5) were not significantly reduced, consistent with our Western blotting data.
