Figure 8.

Cellular target engagement studies for the dual Sirt2/HDAC6 inhibitor 33. (A) Cellular Sirt2 target engagement studies. Representative NanoBRET assay curves displaying the relative Sirt2 affinity of our dual Sirt2/HDAC6 inhibitor 33 in HEK293T cells. 4 and 57 were used as reference compounds for selective Sirt2 and HDAC6 inhibition, respectively. (B) Cellular HDAC6 target engagement studies. MCF-7 cells were treated with vehicle (DMSO) or the selective HDAC6 degrader B4 (62)⁵² (1 or 10 μM) for 6 h. For the cotreatment groups, MCF-7 cells were pretreated with 33 (20 μM) for 30 min and followed by treatment with 62 (1 μM) or 62 (10 μM) for additional 6 h. GAPDH was used as loading control. Representative images of n = 3 replicates.