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. Author manuscript; available in PMC: 2019 Jan 18.
Published in final edited form as: Cell Chem Biol. 2017 Nov 9;25(1):67–77.e3. doi: 10.1016/j.chembiol.2017.09.009

Figure 2. Selective PROTAC-mediated degradation of HER2 and implications for kinome re-wiring.

Figure 2

A – Employing different linker lengths imparts PROTAC selectivity for EGFR over HER2. OVCAR8 cells were treated with PROTAC 1 or 5 for 24 hours before being lysed and probed for EGFR, HER2 and tubulin (as a loading control). B – Cell proliferation assay in SKBr3 cells after 72 hours of treatment with the indicated compound concentrations. C - Treatment of SKBr3 cells with sub-lethal concentrations (500 nM) of PROTAC 1 or diastereomer 2 over 48 hours shows a gradual increase in downstream signalling consistent with kinome re-wiring, previously observed in SKBr3 cells, with diastereomer but not with PROTAC. D – Immunoblotting analysis of c-Met phosphorylation after 48 hours with 500 nM PROTAC 1 or diastereomer 2. See also Figure S2.