c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).
Expert Opin Ther Pat
; 25(8): 849-72, 2015.
Article
en En
| MEDLINE
| ID: mdl-25991433
INTRODUCTION: c-Jun N-terminal kinases (JNKs) are involved in the emergence and progression of diverse pathologies such as neurodegenerative, cardiovascular and metabolic disorders as well as inflammation and cancer. In recent years, several highly selective pan-JNK inhibitors have been characterized and three chemical entities targeting JNKs have been investigated in clinical trials. AREAS COVERED: This review summarizes patents claiming inhibitors of all JNK isoforms published between 2010 and 2014. Although primarily focusing on the patent literature, relevant peer-reviewed publications related to the covered patents have also been included. Moreover, key patents claiming novel applications of previously published chemical entities are reviewed. The article highlights a total of 28 patents from nine pharmaceutical companies and academic research groups. EXPERT OPINION: Although some selective pan-JNK inhibitors with reasonable in vivo profiles are now available, little is known about the isoform selectivity required for each particular indication and the development of isoform-selective JNK inhibitors still represents a challenge in JNK drug discovery. Moreover, isoform-selective tool compounds are a prerequisite to a comprehensive understanding of the biology of each JNK isoform. Potential approaches towards such compounds include the design of type-II and type-I(1)/2 binders, which are absent in the current JNK inhibitor portfolios, as well as the design of novel allosteric inhibitors. Furthermore, covalent inhibition, which already led to the first high-quality probe for JNKs, might be further exploited for gaining selectivity and in vivo efficacy. With regard to a potential therapeutic application, the recently proposed concept of covalent reversible inhibitors is expected to be attractive.
Palabras clave
Alzheimer's disease; Huntington's disease; JNK1; JNK2; JNK3; MAPK kinases; Parkinson's disease; c-Jun N-terminal kinase inhibitors; cancer; cardiovascular disorders; chemical probes; dual leucine zipper kinase; inflammation; isoform selectivity; metabolic disorders; mitogen-activated protein kinase kinase 4; neurodegenerative disorders; p38 MAP kinase; stroke
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
/
Proteínas Quinasas JNK Activadas por Mitógenos
/
Inhibidores de Proteínas Quinasas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Expert Opin Ther Pat
Asunto de la revista:
TERAPEUTICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido