Publications | Allosteric targeting of the Fanconi anemia E2 Ube2T by fragment screening

Ube2T is the E2 ubiquitin-conjugating enzyme of the Fanconi anemia DNA repair pathway and it's overexpressed in several cancers, representing an attractive target for the development of inhibitors. Despite the extensive efforts in targeting the ubiquitin system, very few E2 binders have currently been discovered. Herein we report the identification of a new allosteric pocket on Ube2T through a fragment screening using biophysical methods. Several fragments binding to this site inhibit ubiquitin conjugation in vitro.

Principal Investigator(s):

Author(s):
Morreale, FE., Bortoluzzi, A., Chaugule, V.K., Arkinson, C., Walden, H., Ciulli, A

PubMed:
28437106
Citation:
Morreale, FE., Bortoluzzi, A., Chaugule, V.K., Arkinson, C., Walden, H., Ciulli, A
Journal of Medicinal Chemistry
2017
DOI: 10
1021/acs.jmedchem.7b00147
PMID: 28437106