a, Schematic of the PROTAC strategy. A ternary complex formed upon binding of PROTAC, a target protein (e.g., drug-resistant mutant allele of a selected protein) and an E3 ligase complex can promote target protein ubiquitination (Ub) and degradation by the proteasome.
b, Schematic showing wild-type and drug A-resistant cells (blue and orange, respectively). Wild-type cells are sensitive to inhibition with drug A but not drug B. Cells that acquire resistance to drug A can become collaterally sensitive to drug B.