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Pediatr Res. 2010 May;67(5):505-8. doi: 10.1203/PDR.0b013e3181d35017.

Protacs for treatment of cancer.

Author information

1
Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. kms@ucla.edu

Abstract

Protein degradation is the cell's mechanism of eliminating misfolded or unwanted proteins. The pathway by which proteins are degraded occurs through the ubiquitin-proteasome system. Ubiquitin is a small 9-kD (kDa) protein that is attached to proteins. A minimum of four ubiquitins are required for proteins to be recognized by the degradation machinery, known as the 26S proteasome. Defects in ubiquitination have been identified in a number of diseases, including cancer, neurodegenerative diseases, and metabolic disorders. We sought to exploit the delicate balance between protein synthesis and degradation to treat cancer by designing a chimeric molecule, known as Protac (Proteolysis Targeting Chimeric molecule). Protacs are heterobifunctional nanomolecules that are approximately 10 nm in size and can recruit proteins that cause cancer to the ubiquitin-proteasome machinery for degradation. In this review, we discuss the development of this novel technology for the treatment of cancer.

PMID:
20075761
PMCID:
PMC2881331
DOI:
10.1203/PDR.0b013e3181d35017
[Indexed for MEDLINE]
Free PMC Article

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