Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases.
Eur J Med Chem
; 182: 111646, 2019 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-31521028
ABSTRACT
The immunoproteasome, a specialized form of proteasome, is mainly expressed in lymphocytes and monocytes of jawed vertebrates and responsible for the generation of antigenic peptides for cell-mediated immunity. Overexpression of immunoproteasome have been detected in a wide range of diseases including malignancies, autoimmune and inflammatory diseases. Following the successful approval of constitutive proteasome inhibitors bortezomib, carfilzomib and Ixazomib, and with the clarification of immunoproteasome crystal structure and functions, a variety of immunoproteasome inhibitors were discovered or rationally developed. Not only the inhibitory activities, the selectivities for immunoproteasome over constitutive proteasome are essential for the clinical potential of these analogues, which has been validated by the clinical evaluation of immunoproteasome-selective inhibitor KZR-616 for the treatment of systemic lupus erythematosus. In this review, structure, function as well as the current developments of various inhibitors against immunoproteasome are going to be summarized, which help to fully understand the target for drug discovery.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
/
Neoplasias Hematológicas
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Complejo de la Endopetidasa Proteasomal
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Inhibidores de Proteasoma
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Antineoplásicos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2019
Tipo del documento:
Article
País de afiliación:
China