To investigate the cellular target engagement, the acetylation levels of HDAC substrate proteins like Ac-α-tubulin and Ac-histone H3 were investigated by immunoblot analysis for AP1, AP3, AP4, and Since PROTACs with rigid linkers often improve potency and selectivity in targeted protein degradation, two PROTACs (AP7 and AP8, Figure ) with rigid linkers were designed and synthesized to replace the flexible linker in AP1. Both chosen rigid linkers are similar in length to AP1