2020 年 78 巻 5 号 p. 402-413
New therapeutic modalities are great interests in pharmaceutical researchers. We believe that induction of selective degradation of target proteins by small molecules could become a new therapeutic modality of drug discovery. And we speculated that formation of an artificial (nonphysiological) complex of cIAP1 (cellular inhibitor of apoptosis protein 1) and a target protein would be induced by a hybrid small molecule composed of a cIAP1 ligand linked to a ligand of the target protein, and this would lead to cIAP1-mediated ubiquitination and subsequent proteasomal degradation of the target protein. This review article summarizes advances in chemical protein knockdown, that is, the small hybrid molecules induce decrease of the target proteins in living cells. This article also describes that this technology is capable of degrading receptors, enzymes, substrate binding proteins, and aggregation-prone proteins.