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An overview of the PROTAC targeting EGFR for CRL2VHL-mediated polyubiquitination. (A) 2D structure of the PROTAC MS39 that targets EGFR. The “warhead” potion of the PROTAC is based on EGFR inhibitor (EGFRi) gefitinib. (B) MS39 can recruit EGFR for polyubiquitin conjugation by the CRL2VHL. MS39 mediated EGFR degradation is a catalytic process, as evidenced with dissociation of the PROTAC from the CRL2VHL complex after EGFR polyubiquitination.
