BPR1J-097, a novel FLT3 kinase inhibitor, exerts potent inhibitory activity against AML.
Br J Cancer
; 106(3): 475-81, 2012 Jan 31.
Article
em En
| MEDLINE
| ID: mdl-22187040
ABSTRACT
BACKGROUND:
Activating mutations of Fms-like tyrosine kinase 3 (FLT3) constitute a major driver in the pathogenesis of acute myeloid leukaemia (AML). Hence, pharmacological inhibitors of FLT3 are of therapeutic interest for AML.METHODS:
The effects of inhibition of FLT3 activity by a novel potent FLT3 inhibitor, BPR1J-097, were investigated using in vitro and in vivo assays.RESULTS:
The 50% inhibitory concentration (IC(50)) of BPR1J-097 required to inhibit FLT3 kinase activity ranged from 1 to 10 nM, and the 50% growth inhibition concentrations (GC(50)s) were 21±7 and 46±14 nM for MOLM-13 and MV4-11 cells, respectively. BPR1J-097 inhibited FLT3/signal transducer and activator of transcription 5 phosphorylation and triggered apoptosis in FLT3-driven AML cells. BPR1J-097 also showed favourable pharmacokinetic property and pronounced dose-dependent tumour growth inhibition and regression in FLT3-driven AML murine xenograft models.CONCLUSION:
These results indicate that BPR1J-097 is a novel small molecule FLT-3 inhibitor with promising in vivo anti-tumour activities and suggest that BPR1J-097 may be further developed in preclinical and clinical studies as therapeutics in AML treatments.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
/
Benzamidas
/
Leucemia Mieloide Aguda
/
Inibidores de Proteínas Quinases
/
Tirosina Quinase 3 Semelhante a fms
Limite:
Animals
/
Humans
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Male
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Taiwan