Design and synthesis of novel site-specific antibody-drug conjugates that target TROP2.
Bioorg Med Chem
; 110: 117828, 2024 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-38981219
ABSTRACT
The approval of Trodelvy® validates TROP2 as a druggable but challenging target for antibody-drug conjugates (ADCs) to treat metastatic triple-negative breast cancer (mTNBC). Here, based on the TROP2-targeted antibody sacituzumab, we designed and developed several site-specific ADC candidates, which employ MMAE (monomethyl auristatin E) as the toxin, via IgG glycoengineering or affinity-directed traceless conjugation. Systematic evaluation of these site-specific ADCs in homogeneity, hydrophilicity, stability, and antitumor efficiency was conducted. The results indicate that the site-specific ADCs gsADC 3b made from one-step glycoengineering exhibit good aggregation stability and in vivo efficacy, providing a new format of ADCs that target TROP2.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
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Moléculas de Adesão Celular
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Imunoconjugados
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Antígenos de Neoplasias
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Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Bioorg Med Chem
/
Bioorg. med. chem
/
Bioorganic & medicinal chemistry
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article