RGD Reference Report - BPR1J-097, a novel FLT3 kinase inhibitor, exerts potent inhibitory activity against AML. - Rat Genome Database

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BPR1J-097, a novel FLT3 kinase inhibitor, exerts potent inhibitory activity against AML.

Authors: Lin, WH  Jiaang, WT  Chen, CW  Yen, KJ  Hsieh, SY  Yen, SC  Chen, CP  Chang, KY  Chang, CY  Chang, TY  Huang, YL  Yeh, TK  Chao, YS  Chen, CT  Hsu, JT 
Citation: Lin WH, etal., Br J Cancer. 2012 Jan 31;106(3):475-81. doi: 10.1038/bjc.2011.564. Epub 2011 Dec 20.
RGD ID: 11049503
Pubmed: PMID:22187040   (View Abstract at PubMed)
PMCID: PMC3273346   (View Article at PubMed Central)
DOI: DOI:10.1038/bjc.2011.564   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FLT3Humanacute myelomonocytic leukemia treatmentIMP  RGD 
Flt3Ratacute myelomonocytic leukemia treatmentISOFLT3 (Homo sapiens) RGD 
Flt3Mouseacute myelomonocytic leukemia treatmentISOFLT3 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Flt3  (Fms related receptor tyrosine kinase 3)

Genes (Mus musculus)
Flt3  (FMS-like tyrosine kinase 3)

Genes (Homo sapiens)
FLT3  (fms related receptor tyrosine kinase 3)


Additional Information