Figure 7.

Click and release PROteolysis-Targeting Chimeras (crPROTACs) for BRD4 degradation. (A) Schematic description of click and release of PROTACs by iEDDA medicated uncaging mechanism. (B) In vitro activation of TCO-ARV771 by tetrazine functionalized cancer cell surface. (C) UPLC spectra of release of ARV771 by incubating Ac₄ManNTz (1) and TCO-ARV771 for 2, 4, and 6 h. (D) Release profile of reaction of Ac₄ManNTz (1) (40 μmol/L) with TCO-ARV771 (20 μmol/L). A 20 μL aliquot sample was taken from the reaction mixture for UPLC analysis. Data are averages ± SEM, n = 3. (E) Western blot analysis of BRD4 degradation and c-Myc expression. (F) Quantification of BRD4 protein expression. (G) Quantification of c-Myc protein expression. Data are averages ± SEM, n = 3.