Development of fluorophore labeled or biotinylated anticancer small molecule NSC243928.
Bioorg Med Chem
; 79: 117171, 2023 02 01.
Article
em En
| MEDLINE
| ID: mdl-36680947
ABSTRACT
Small molecule NSC243928 binds with LY6K, a potential target for the treatment of triple-negative breast cancer, and induces cancer cell death with an unclear mechanism. We have developed chemical tools to identify the molecular mechanisms of NSC243928-LY6K interaction. Herein, we report on the development and synthesis of biotinylated and fluorophore-tethered derivatives of NSC243928 guided by docking studies and molecular dynamics. Surface plasmon resonance assay indicates that these derivatives retained a direct binding with LY6K protein. Confocal analysis revealed that nitrobenzoxadiazole (NBD) fluorophore tagged NSC243928 is retained in LY6K expressing cancer cells. These novel modified compounds will be employed in future in vitro and in vivo studies to understand the molecular mechanisms of NSC243928 mediated cancer cell death. These studies will pave the path for developing novel targeted therapeutics and understanding any potential side-effects of these treatments for hard-to-treat cancers such as triple-negative breast cancer or other cancers with high expression of LY6K.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Mama Triplo Negativas
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article