TY  - JOUR
A1  - Chen, Dan
A1  - Gehringer, Matthias
A1  - Lorenz, Sonja
T1  - Developing Small-Molecule Inhibitors of HECT-Type Ubiquitin Ligases for Therapeutic Applications: Challenges and Opportunities
T2  - ChemBioChem
N2  - The ubiquitin system regulates countless physiological and disease-associated processes and has emerged as an attractive entryway for therapeutic efforts. With over 600 members in the human proteome, ubiquitin ligases are the most diverse class of ubiquitylation enzymes and pivotal in encoding specificity in ubiquitin signaling. Although considerable progress has been made in the identification of small molecules targeting RING ligases, relatively little is known about the “druggability” of HECT (homologous to E6AP C terminus) ligases, many of which are critically implicated in human pathologies. A major obstacle to optimizing the few available ligands is our incomplete understanding of their inhibitory mechanisms and the structural basis of catalysis in HECT ligases. Here, we survey recent approaches to manipulate the activities of HECT ligases with small molecules to showcase the particular challenges and opportunities these enzymes hold as therapeutic targets.
KW  - drug discovery
KW  - enzymes
KW  - inhibitors
KW  - reaction mechanisms
KW  - structure-activity relationships
KW  - ubiquitin
Y1  - 2018
UR  - https://opus.bibliothek.uni-wuerzburg.de/opus4-wuerzburg/frontdoor/index/index/docId/22241
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-222412
VL  - 19
ER  -