The positive control A6 achieved significant HDAC6 degradation under both light and dark conditions. PHOTAC 11 displayed significant HDAC6 degradation both in the presence and absence of light, likely due to its relatively long and flexible linker. The linker-less PHOTAC 13 failed to degrade HDAC6 in the dark or after irradiation with UV light. In contrast, PHOTAC 12 with a relatively short γ-aminobutyric acid linker was unable to degrade HDAC6 in the dark (<10% Dmax), but showed a pronounced and significant degradation of HDAC6 with a Dmax of ~50% at 1 µM concentration upon irradiation with UV light. These results indicate that the cisstate of PHOTAC 12 is an active degrader, while the trans-state is nearly inactive (<10% Dmax). To explore the differential activities of the cis-and trans-state of PHOTAC 12, we monitored ternary complex formation through TR-FRET between purified CRBN-DDB1ΔB and HDAC6.