BPR1J-097

• CAT Number: I001246
• CAS Number: 1327167-19-0
• Molecular Formula: C27H28N6O3S
• Molecular Weight: 516.61
• Purity: ≥95%
• Target: Flt3 inhibitor
• Solubility: DMSO:32mg/mL
• Storage: Store at +4C
• IC50: 11±7 nM(Flt3);3 nM (FLT-3 D835Y) [1]
• InChI: InChI=1S/C27H28N6O3S/c1-32-14-16-33(17-15-32)23-12-10-20(11-13-23)27(34)28-26-19-25(29-30-26)21-6-5-7-22(18-21)31-37(35,36)24-8-3-2-4-9-24/h2-13,18-19,31H,14-17H2,1H3,(H2,28,29,30,34)
• InChIKey: RRKKHABFIOHAOI-UHFFFAOYSA-N
• SMILES: O=C(NC1=CC(C2=CC=CC(NS(=O)(C3=CC=CC=C3)=O)=C2)=NN1)C4=CC=C(N5CCN(C)CC5)C=C4

BPR1J-097 is a novel small molecule FLT-3 inhibitor(IC50=11±7 nM) with promising in vivo anti-tumour activities; inhibits FLT-3 D835Y with an IC50 of 3 nM.IC50 value: 11±7 nM(Flt3);3 nM (FLT-3 D835Y) [1]Target: Flt3 inhibitorThe 50% inhibitory concentration (IC50) of BPR1J-097 required to inhibit FLT3 kinase activity ranged from 1 to 10 nM, and the 50% growth inhibition concentrations (GC50s) 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.

Reference

1:Br J Cancer. 2012 Jan 31;106(3):475-81. doi: 10.1038/bjc.2011.564. Epub 2011 Dec 20. BPR1J-097, a novel FLT3 kinase inhibitor, exerts potent inhibitory activity against AML.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, PMID: 22187040 PMCID: PMC3273346 DOI: 10.1038/bjc.2011.564 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.