To validate that the unsymmetric Homo-PROTAC H2-H4 is indeed capable of inducing both ternary complex formation and VHL degradation, we synthesized this hit independently for biological testing (see synthesis overview in Scheme S2). As with the initial set of synthesized Homo-PROTACs, native gel electrophoresis was used to evaluate H2-H4's ability to induce VCB2:H2-H4 ternary complex formation in vitro (Figure &). Incubation of VCB with H2-H4 for 30 min led to quantitative formation of the ternary complex, while SH2 only induced incomplete ternary complex formation under these conditions.