594983-83-2Relevant academic research and scientific papers
FUSED RING HETEROARYL KINASE INHIBITORS
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Page/Page column 63-65, (2010/04/30)
Provided herein are fused ring heteroaryl compounds useful in a variety of methods, including reducing the activity of certain kinases and treating certain disease states.
A small molecule inhibitor selective for a variant ATP-binding site of the chaperonin GroEL
Chapman, Eli,Farr, George W.,Furtak, Krystyna,Horwich, Arthur L.
scheme or table, p. 811 - 813 (2009/09/25)
The chaperonin GroEL is a megadalton-sized molecular machine that plays an essential role in the bacterial cell assisting protein folding to the native state through actions requiring ATP binding and hydrolysis. A combination of medicinal chemistry and genetics has been employed to generate an orthogonal pair, a small molecule that selectively inhibits ATPase activity of a GroEL ATP-binding pocket variant. An initial screen of kinase-directed inhibitors identified an active pyrazolo-pyrimidine scaffold that was iteratively modified and screened against a collective of GroEL nucleotide pocket variants to identify a cyclopentyl carboxamide derivative, EC3016, that specifically inhibits ATPase activity and protein folding by the GroEL mutant, I493C, involving a side chain positioned near the base of ATP. This orthogonal pair will enable in vitro studies of the action of ATP in triggering activation of GroEL-mediated protein folding and might enable further studies of GroEL action in vivo. The approach originated for studying kinases by Shokat and his colleagues may thus also be used to study large macromolecular machines.
CHEMICAL COMPOUNDS
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Page/Page column 40, (2008/06/13)
Pyrazole derivatives are described herein. The described invention also includes methods of making such pyrazole derivatives as well as methods of using the same in the treatment of diseases.
