Design, synthesis, and biological evaluation of F-18-labelled 2, 4-diaminopyrimidine-type FAK-targeted inhibitors as potential tumour imaging agents.
Bioorg Med Chem Lett
; 30(19): 127452, 2020 10 01.
Article
en En
| MEDLINE
| ID: mdl-32736076
ABSTRACT
As a type of intracellular nonreceptor tyrosine kinase, focal adhesion kinase (FAK) can be highly expressed in most types of tumours and is thus regarded as a promising antitumour target. In this study, a series of novel 2,4-diaminopyrimidine FAK-targeted inhibitors were designed, synthesized and characterized by 1H NMR, 13C HNMR, and HRMS spectra. These compounds, with an IC50 range of 5.0-205.1 nM, showed superior inhibitory activity against FAK. Two compounds, [18F]Q-2 and [18F]Q-4, with respective IC50 values of 5.0 nM and 21.6 nM, were labelled by 18F, accompanied by evaluation of their biodistributions. For [18F]Q-2, at 30 min post-injection, promising target-to-nontarget ratios were observed, associated with tumour/blood, tumour/muscle, and tumour/bone ratios of 1.17, 2.99 and 2.19, respectively. The results indicated that [18F]Q-2 is a potential PET tracer for tumour diagnosis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Radiofármacos
/
Inhibidores de Proteínas Quinasas
/
Quinasa 1 de Adhesión Focal
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Aminopiridinas
/
Neoplasias
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China