Lysophosphatidic Acid Receptor 1 (LPA1) Antagonists as Potential Migrastatics for Triple Negative Breast Cancer.
ChemMedChem
; 19(16): e202400013, 2024 Aug 19.
Article
em En
| MEDLINE
| ID: mdl-38648251
ABSTRACT
Metastasis is responsible for about 90 % of cancer deaths. Anti-metastatic drugs, termed as migrastatics, offer a distinctive therapeutic approach to address cancer migration and invasion. However, therapeutic exploitation of metastasis-specific targets remains limited, and the effective prevention and suppression of metastatic cancer continue to be elusive. Lysophosphatidic acid receptor 1 (LPA1) is activated by an endogenous lipid molecule LPA, leading to a diverse array of cellular activities. Previous studies have shown that the LPA/LPA1 axis supports the progression of metastasis for many types of cancer. In this study, we report the synthesis and biological evaluation of fluorine-containing triazole derivatives as potent LPA1 antagonists, offering potential as migrastatic drugs for triple negative breast cancer (TNBC). In particular, compoundâ
12 f, the most potent and highly selective in this series with an IC50 value of 16.0â
nM in the cAMP assay and 18.4â
nM in the calcium mobilization assay, inhibited cell survival, migration, and invasion in the TNBC cell line. Interestingly, the compound did not induce apoptosis in TNBCâ
cells and demonstrated no cytotoxic effects. These results highlight the potential of LPA1 as a migrastatic target. Consequently, the LPA1 antagonists developed in this study hold promise as potential migrastatic candidates for TNBC.
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Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
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Receptores de Ácidos Lisofosfatídicos
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Neoplasias de Mama Triplo Negativas
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Antineoplásicos
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article