Discovery of new quinazoline derivatives as irreversible dual EGFR/HER2 inhibitors and their anticancer activities - Part 1.
Bioorg Med Chem Lett
; 29(4): 591-596, 2019 02 15.
Article
en En
| MEDLINE
| ID: mdl-30600209
ABSTRACT
Overexpression of EGFR and HER2 are observed in many breast, ovarian, colon and prostate cancers. The second and third generation irreversible EGFR/HER2 dual kinase inhibitors became popular after the approval of Afatinib by FDA to overcome the mutation related problem. To find efficacious drug candidates, a series of novel quinazoline derivatives were designed, synthesized and evaluated as dual EGFR/HER2 tyrosine kinase (TK) inhibitors. Selected twenty four compounds were reported here with significant inhibitory activities against EGFR/HER2 tyrosine kinases. Several compounds showed nanomolar IC50 values. In vitro studies of quinazoline derivatives were done on NCI-H1975, HCC827, A431, MDA MB-453 cell lines. The compounds 1a, 1d and 1v were found more potent compared to standard drug afatinib. In vivo efficacy study of 1d on nude mice NCI-H1975 tumour xenograft model was discussed.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Quinazolinas
/
Receptor ErbB-2
/
Descubrimiento de Drogas
/
Receptores ErbB
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article