Potency assay, off target (cells):
To investigate the degradation selectivity of CBPD-268 on a global level in an unbiased manner, a proteomic analysis of CBPD-268 in the VCaP cell line was performed with 1 nM of CBPD-268 for 4 h.
Probe Selectivity in
Cell:
CBPD-268 showed a profound and significant depletion of CBP/p300 proteins, with the CBP and p300 protein levels reduced by 75% and 69%, respectively. Several other proteins, including NKX3-1, ZFYVE19, BUB1B, OXLD1, USHBP1, and BRD2, were also reduced moderately. NKX3-1 is an AR target gene, and its expression is coregulated by CBP/p300. GSPT1, one of the previously reported neo-substrates for CRBN based PROTAC degrader, was not reduced by CBPD-268 in the proteomic study, which was further confirmed by Western blotting analysis.
