438204-56-9Relevant academic research and scientific papers
Tuning a three-component reaction for trapping kinase substrate complexes
Statsuk, Alexander V.,Maly, Dustin J.,Seeliger, Markus A.,Fabian, Miles A.,Biggs, William H.,et al.
supporting information; experimental part, p. 17568 - 17574 (2009/09/08)
The upstream protein kinases responsible for thousands of phosphorylation events in the phosphoproteome remain to be discovered. We developed a three-component chemical reaction which converts the transient noncovalent substrate-kinase complex into a covalently cross-linked product by utilizing a dialdehyde-based cross-linker, 1. Unfortunately, the reaction of 1 with a lysine in the kinase active site and an engineered cysteine on the substrate to form an isoindole cross-linked product could not be performed in the presence of competing cellular proteins due to nonspecific side reactions. In order to more selectively target the cross-linkerto protein kinases in cell lysates, we replaced the weak, kinase- bindi ng adenosine moiety of 1 with a potent protein kinase inhibitor scaffold. In addition, we replaced the o-phthaldialdehyde moiety in 1 with a less-reactive thiophene-2,3-dicarboxaldehyde moiety. The combination of these two structural modifications provides for cross-linking of a cysteine-containing substrate to its corresponding kinase in the presence of competing cellular proteins.
Pyrazole compounds useful as protein kinase inhibitors
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Page/Page column 141, (2008/06/13)
This invention describes novel pyrazole compounds of formula IIIa: wherein R1 is T-Ring D, wherein Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; Rx/sup
