生細胞内の疾患関連タンパク質を 減少させる低分子創薬手法の開発

Translated title of the contribution: Degradation of disease related proteins in living cells by small molecules

Minoru Ishikawa, Yuichi Hashimoto

Research output: Contribution to journalArticle

Abstract

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.

Translated title of the contributionDegradation of disease related proteins in living cells by small molecules
Original languageJapanese
Pages (from-to)402-413
Number of pages12
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume78
Issue number5
DOIs
Publication statusPublished - 2020 Jan 1

ASJC Scopus subject areas

  • Organic Chemistry

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