Proteolysis targeting chimeras (PROTACs) are dual-functional hybrid molecules that can selectively recruit an E3 ubiquitin ligase to a target protein to direct the protein into the ubiquitinproteasome system (UPS),thereby selectively reducing the target protein level by the ubiquitinproteasome pathway.Nowadays,small-molecule PROTACs are gaining popularity as tools to degrade pathogenic protein.Herein,we present the first small-molecule PROTACs that can induce the α1A-adrenergic receptor (α1A-AR) degradation,which is also the first small-molecule PROTACs for G proteincoupled receptors (GPCRs) to our knowledge.These degradation inducers were developed through conjugation of known α1-adrenergic receptors (α1-ARs) inhibitor prazosin and cereblon (CRBN) ligand pomalidomide through the different linkers.The representative compound 9c is proved to inhibit the proliferation of PC-3 cells and result in tumor growth regression,which highlighted the potential of our st.udy as a new therapeutic strategy for prostate cancer.