Discovery of IDO1 and DNA dual targeting antitumor agents.
Org Biomol Chem
; 15(47): 9992-9995, 2017 Dec 06.
Article
em En
| MEDLINE
| ID: mdl-29177308
ABSTRACT
The development of small molecules for cancer immunotherapy is highly challenging and indoleamine 2,3-dioxygenase 1 (IDO1) represents a promising target. Inspired by the synergistic effects between IDO1 inhibitors and traditional antitumor chemotherapeutics, the first orally active dual IDO1 and DNA targeting agents were designed by the pharmacophore fusion strategy. The bifunctional hybrids exhibited enhanced IDO1 enzyme inhibitory activity and in vitro cytotoxicity as compared to IDO1 inhibitor 1-methyl-tryptophan and DNA alkylating agent melphalan. In a murine LLC tumor model, the dual targeting agents demonstrated excellent antitumor efficacy, highlighting the advantages of this novel design strategy to improve the efficacy of small molecule cancer immunotherapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Triptofano
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DNA de Neoplasias
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Inibidores Enzimáticos
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Indolamina-Pirrol 2,3,-Dioxigenase
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Melfalan
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article