Figure 4 |. Cell line dependency and modular design of HDAC3-targeted degraders.

(A) Heatmap displaying the log₂FC in relative abundance for HDACs in response to treatment with indicated degraders in KELLY and MM.1S cell lines. (B) Scatterplots depicting the log₂FC in relative protein abundance in response to treatment with XY-07-093 in KELLY and MM.1S cells. (C) As in B but treated with XY-07-189. (D) Chemical structures of dacinostat-VHL1 degraders with hydroxamate or benzamide zinc-binding groups. (E) Heatmap displaying HDAC in vitro enzymatic inhibition data (pIC₅₀) comparing HDAC selectivity for hydroxamate- (XY-07-093) and benzamide-based (XY-07-155) molecules. Inhibition data is from n = 1 ten-point titrations. (F) Scatterplot depicting the log₂FC in relative protein abundance in response to treatment with XY-08–012. Proteomics data is from n = 1–2 biological replicates. * on proteomics heatmaps indicates a P-value < 0.001. See also Table S2–3, Figure S1, S3, S4.