Cited 4 time in webofscience Cited 9 time in scopus

Chemically Induced Cellular Proteolysis: An Emerging Therapeutic Strategy for Undruggable Targets

Title
Chemically Induced Cellular Proteolysis: An Emerging Therapeutic Strategy for Undruggable Targets
Authors
Moon, SeonghyeonLee, Byung Hoon
DGIST Authors
Lee, Byung Hoon
Issue Date
2018-11
Citation
Molecules and Cells, 41(11), 933-942
Type
Article
Article Type
Review
Author Keywords
deubiquitinating enzymeinduced proteolysisPROTACsmall-moleculesubiquitin-proteasome systemundruggable target
Keywords
SMALL-MOLECULE INHIBITORUBIQUITIN-PROTEASOME SYSTEMPROTEIN-DEGRADATIONDEUBIQUITINASE INHIBITORMEDIATED DEGRADATIONCANCERDISCOVERYKNOCKDOWNPOTENTRECEPTOR
ISSN
1016-8478
Abstract
Traditionally, small-molecule or antibody-based therapies against human diseases have been designed to inhibit the enzymatic activity or compete for the ligand binding sites of pathological target proteins. Despite its demonstrated effectiveness, such as in cancer treatment, this approach is often limited by recurring drug resistance. More importantly, not all molecular targets are enzymes or receptors with druggable ‘hot spots’ that can be directly occupied by active site-directed inhibitors. Recently, a promising new paradigm has been created, in which small-molecule chemicals harness the naturally occurring protein quality control machinery of the ubiquitin-proteasome system to specifically eradicate diseasecausing proteins in cells. Such ‘chemically induced protein degradation’ may provide unprecedented opportunities for targeting proteins that are inherently undruggable, such as structural scaffolds and other non-enzymatic molecules, for therapeutic purposes. This review focuses on surveying recent progress in developing E3-guided proteolysis-targeting chimeras (PROTACs) and small-molecule chemical modulators of deubiquitinating enzymes upstream of or on the proteasome.
URI
http://hdl.handle.net/20.500.11750/9485
DOI
10.14348/molcells.2018.0372
Publisher
한국분자세포생물학회
Related Researcher
  • Author Lee, Byung-Hoon Lab of Protein Homeostasis and Drug Discovery
  • Research Interests Ubiquitin-proteasome system; Protein homeostasis; Small-molecule chemical screening and drug discovery in human disease
Files:
There are no files associated with this item.
Collection:
Department of New BiologyLab of Protein Homeostasis and Drug Discovery1. Journal Articles


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