Discovery of a septin-4 covalent binder with antimetastatic activity in a mouse model of melanoma.
Bioorg Chem
; 144: 107164, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-38306824
ABSTRACT
Cancer spreading through metastatic processes is one of the major causes of tumour-related mortality. Metastasis is a complex phenomenon which involves multiple pathways ranging from cell metabolic alterations to changes in the biophysical phenotype of cells and tissues. In the search for new effective anti-metastatic agents, we modulated the chemical structure of the lead compound AA6, in order to find the structural determinants of activity, and to identify the cellular target responsible of the downstream anti-metastatic effects observed. New compounds synthesized were able to inhibit in vitro B16-F10 melanoma cell invasiveness, and one selected compound, CM365, showed in vivo anti-metastatic effects in a lung metastasis mouse model of melanoma. Septin-4 was identified as the most likely molecular target responsible for these effects. This study showed that CM365 is a promising molecule for metastasis prevention, remarkably effective alone or co-administered with drugs normally used in cancer therapy, such as paclitaxel.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_malignant_skin_melanoma
/
6_other_respiratory_diseases
/
6_trachea_bronchus_lung_cancer
Asunto principal:
Melanoma Experimental
/
Neoplasias Pulmonares
Límite:
Animals
Idioma:
En
Revista:
Bioorg Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia