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Chem Biol ; 21(11): 1433-43, 2014 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-25442375

RESUMO

The c-Jun N-terminal kinase (JNK) family, with its three members JNK1, JNK2, and JNK3, is a subfamily of mitogen-activated protein kinases. Involved in many aspects of cellular processes, JNK has been also associated with pathological states such as neurodegenerative diseases, inflammation, and cancers. In oncology, each isoform plays a distinct role depending on the context of the targeted tissue/organ, the tumor stage, and, most likely, the signaling pathway activated upstream. Consequently, the current challenge in finding new successful anti-JNK therapies is to design isoform-selective inhibitors of the JNKs. In this review, a particular focus is given to the JNK inhibitors that have been developed thus far when examining 3D structures of various JNK-inhibitor complexes. Using current data regarding structure-activity relationships and medicinal chemistry approaches, our objective is to provide a better understanding of the design and development of selective JNK inhibitors in the present and future.


Assuntos
Antineoplásicos/química , Desenho de Fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Antineoplásicos/uso terapêutico , Ligação Competitiva , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Relação Estrutura-Atividade
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