Will downstream function of E3 ligand in protac influences the hook effect and Dmax ?

01 January 1970 0 6K Report

When developing PROTACs, I find some CRBN target PROTAC molecules showed weaker hook effect with weaker degradation in CRBN induced IKZF. I wonder whether the downstream function of E3 ligand as a 'moleculae glue' compete with the ternary complex formation.

Does anyone have similar experience?

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