Potency assay, off target (cells):
Global Degradation Proteomic Analysis of TO-1187: MM.1S cells were exposed to two different concentrations (10 nM and 100 nM) of TO-1187, and cell pellets were collected after a 6 h incubation period.
Probe Selectivity in
Cell:
At a concentration of 100 nM, TO-1187 exhibited a distinct degradation pattern. Specifically, TO-1187 caused a substantial reduction in the levels of HDAC6 protein without affecting the levels of other proteins including other HDACs. //no decrease was also observed in the protein levels of prominent IMiD-based neosubstrates, including IKZF1, IKZF3, CK1α, and GSPT1, demonstrating the specificity of TO-1187 for HDAC6 degradation.
At a lower concentration of 10 nM, TO-1187 had no appreciable impact on the overall abundance of any of the cellular proteins detected and quantified.
