Generic placeholder image

Current Cancer Drug Targets


ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy

Author(s): Nobumichi Ohoka, Norihito Shibata, Takayuki Hattori and Mikihiko Naito

Volume 16, Issue 2, 2016

Page: [136 - 146] Pages: 11

DOI: 10.2174/1568009616666151112122502

Price: $65


Selective degradation of pathogenic proteins by small molecules in cells is a novel approach for development of therapeutic agents against various diseases, including cancer. We and others have developed a protein knockdown technology with a series of hybrid small compounds, called SNIPERs (Specific and Nongenetic IAP-dependent Protein ERasers); and peptidic chimeric molecules, called PROTACs (proteolysis-targeting chimeric molecules), which induce selective degradation of target proteins via the ubiquitin-proteasome pathway. These compounds include two different ligands connected by a linker; one is a ligand for a ubiquitin ligase and the other is a ligand for the target protein, which are expected to crosslink these proteins in cells. Theoretically, any cytosolic protein can be targeted for degradation by this technology. To date, several SNIPERs and PROTACs against various oncogenic proteins have been developed, which specifically induce polyubiquitylation and proteasomal degradation of the oncogenic proteins, resulting in cell death, growth arrest, or impaired migration of cancer cells. Thus, this protein knockdown technology has a great potential for cancer therapy.

Keywords: IAP, PROTAC (proteolysis-targeting chimeric molecule), proteasome, protein knockdown, SNIPER (Specific and Nongenetic IAP-dependent Protein ERasers), ubiquitin ligase.

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy