After irradiation with 390 nm light (cis-state), PHOTAC 12 led to approximately 2-fold increase in ternary complex between CRBN and HDAC6 compared to 505 nm condition (trans-state) (Figure ), which explains the reduced degradation in a cellular environment. Our prior experiments showed that 390 nm irradiation results in ~65% transition to cis-state (Figure ), while 505 nm light results in near 95% transition to trans-state indicating that the pure cisstate would result in even higher ternary complex formation. To gain deeper insights on a molecular level, we performed modeling studies utilizing an established protocol for ternary complex modeling. To this end, crystal structures of HDAC6 (PDB ID: 5EEI) and CRBN (PDB ID: 4CI2) were selected as templates. The results (Figure ) demonstrate that both cis-and trans-states of PHOTAC 12 are capable of forming distinct ternary complexes with HDAC6 and CRBN. Specifically, the HDAC warhead in both states of PHOTAC 12 engages in metal chelation with Zn 2+ within the HDAC6 pocket. In addition, the CRBN warhead of PHOTAC 12 in both states forms hydrogen bonds with N353, H380, and W382 within the CRBN binding pocket, which are crucial for CRBN recruitment. These interactions provide the basis for ternary complex formation and corroborate the findings from immunoblot analysis and TR-FRET assay.