Synthesis and Structural Optimization of ATG4B Inhibitors for the Attenuation of Autophagy in Glioblastoma.
ACS Med Chem Lett
; 15(2): 258-264, 2024 Feb 08.
Article
em En
| MEDLINE
| ID: mdl-38352843
ABSTRACT
Glioblastoma, a prevalent malignant CNS tumor, presents a therapeutic challenge because of resistance to standard treatments, including radiation therapy and temozolomide. Both modalities induce autophagy, thereby paradoxically promoting tumor survival. The cysteine protease ATG4B is implicated in this cellular process, which highlights the enzyme as a viable therapeutic target for glioblastoma. We have developed streamlined syntheses for ATG4B inhibitor NSC185058, its derivatives, and fluorogenic ATG4B substrate pim-FG-PABA-AMC. We leveraged these findings to rapidly identify novel compound MJO445, which demonstrates markedly greater potency biochemically and in cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2024
Tipo de documento:
Article