Discovery and Characterization of PROTACs Targeting Tissue Transglutaminase (TG2).
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
27 07 2023
27 07 2023
Historique:
medline:
28
7
2023
pubmed:
14
7
2023
entrez:
14
7
2023
Statut:
ppublish
Résumé
Tissue transglutaminase (TG2) is a multifunctional enzyme involved in the cross-linking of extracellular matrix proteins, formation of complexes with fibronectin (FN) and integrins, and GTP hydrolysis. TG2 is activated in several pathological conditions, including cancer. We recently described a novel series of ligands that bind to TG2 and inhibit its interaction with FN. Because TG2 acts via multiple mechanisms, we set out to pursue a targeted protein degradation strategy to abolish TG2's myriad functions. Here, we report the synthesis and characterization of a series of VHL-based degraders that reduce TG2 in ovarian cancer cells in a proteasome-dependent manner. Degradation of TG2 resulted in significantly reduced cancer cell adhesion and migration
Identifiants
pubmed: 37449845
doi: 10.1021/acs.jmedchem.2c01859
pmc: PMC10388319
doi:
Substances chimiques
Protein Glutamine gamma Glutamyltransferase 2
EC 2.3.2.13
Transglutaminases
EC 2.3.2.13
Proteolysis Targeting Chimera
0
GTP-Binding Proteins
EC 3.6.1.-
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
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