Acylideneoxoindoles: a new class of reversible inhibitors of human transglutaminase 2.
Bioorg Med Chem Lett
; 21(9): 2692-6, 2011 May 01.
Article
in En
| MEDLINE
| ID: mdl-21215619
ABSTRACT
Inhibitors of human transglutaminase 2 (TG2) are anticipated to be useful in the therapy of a variety of diseases including celiac sprue as well as certain CNS disorders and cancers. A class of 3-acylidene-2-oxoindoles was identified as potent reversible inhibitors of human TG2. Structure-activity relationship analysis of a lead compound led to the generation of several potent, competitive inhibitors. Analogs with significant non-competitive character were also identified, suggesting that the compounds bind at one or more allosteric regulatory sites on this multidomain enzyme. The most active compounds had K(i) values below 1.0 µM in two different kinetic assays for human TG2, and may therefore be suitable for investigations into the role of TG2 in physiology and disease in animals.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transglutaminases
/
GTP-Binding Proteins
/
Enzyme Inhibitors
/
Indoles
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2011
Type:
Article
Affiliation country:
United States