Fig. 6: Proteomic analysis showing RC-1 selectively degrades BTK. | Nature Communications

Fig. 6: Proteomic analysis showing RC-1 selectively degrades BTK.

From: Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry

Fig. 6

MOLM-14 cells were treated with either compounds (200 nM a RC-1, b RNC-1, c IRC-1, or d RC-1-Me (RC-1 non-degrader control)) or DMSO for 24 h. Lysates were treated with a TMT-10plex kit and subjected to mass spec-based proteomics analysis. Datasets represent an average of duplicates. Volcano plot shows protein abundance (log2) as a function of significance level (log10). Nonaxial vertical lines denote abundance changes from 0.7 to 1.4 (i.e. 2±0.5), whereas nonaxial horizontal line marks P = 0.05 significance threshold. Downregulated proteins of significance are found in the upper left quadrant of the plots. Violet red dots represent kinases. Dark blue dots represent zinc-finger proteins. Both RNC-1 and IRC-1 showed significant degradation of 7 kinases, while RC-1 only degrades BTK and CSK. A total of 7280 proteins were identified, and only the ones with at least one uniquely identified peptide are displayed. The raw data are provided as Supplementary Data 2.

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