A new delivery system for auristatin in STxB-drug conjugate therapy.
Eur J Med Chem
; 95: 483-91, 2015 May 05.
Article
en En
| MEDLINE
| ID: mdl-25847766
ABSTRACT
A key challenge in anticancer therapy is to gain control over the biodistribution of cytotoxic drugs. The most promising strategy consists in conjugating drugs to tumor-targeting carriers, thereby combining high cytotoxic activity and specific delivery. To target Gb3-positive cancer cells, we exploit the non-toxic B-subunit of Shiga toxin (STxB). Here, we have conjugated STxB to highly potent auristatin derivatives (MMA). A former linker was optimized to ensure proper drug-release upon reaching reducing environments in target cells, followed by a self-immolation step. Two conjugates were successfully obtained, and in vitro assays demonstrated the potential of this targeting system for the selective elimination of Gb3-positive tumors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Portadores de Fármacos
/
Toxina Shiga
/
Aminobenzoatos
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2015
Tipo del documento:
Article
País de afiliación:
Francia