1310495-85-2Relevant academic research and scientific papers
3-ACYLIDENE-2-OXOINDOLE DERIVATIVES FOR INHIBITION OF TRANSGLUTAMINASE 2
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Page/Page column 52, (2012/06/30)
Provided herein are acylidene oxoindole derivatives, compositions including them, and methods of inhibiting transglutaminase 2 and treating diseases mediated by transglutaminase 2 by administering such derivatives and compositions.
Acylideneoxoindoles: A new class of reversible inhibitors of human transglutaminase 2
Kl?ck, Cornelius,Jin, Xi,Choi, Kihang,Khosla, Chaitan,Madrid, Peter B.,Spencer, Andrew,Raimundo, Brian C.,Boardman, Paul,Lanza, Guido,Griffin, John H.
supporting information; experimental part, p. 2692 - 2696 (2011/06/20)
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 Ki 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.
