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MedKoo CAT#: 401161
Description: BPR1J-097 is a novel small molecule FLT-3 inhibitor with promising in vivo anti-tumour activities. BPR1J-097 may be useful in AML treatments.IC50 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 21Â±7 and 46Â±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.
MedKoo Cat#: 401161
Chemical Formula: C27H28N6O3S
Exact Mass: 516.19436
Molecular Weight: 516.61
Elemental Analysis: C, 62.77; H, 5.46; N, 16.27; O, 9.29; S, 6.21
Synonym: BPR1J097; BPR1J-097; BPR1J 097; BPR1-J097; BPR1 J097; BPR1J097
IUPAC/Chemical Name: 4-(4-methylpiperazin-1-yl)-N-(3-(3-(phenylsulfonamido)phenyl)-1H-pyrazol-5-yl)benzamide.
InChi Key: RRKKHABFIOHAOI-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: 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 was discovered by a rational design strategy. BPR1J-097 with a novel sulphonamide pharmacophore exhibits potent FLT3-inhibitory activity and has potent growth-inhibitory effects on FLT3-ITD leukaemic cells. According to our SAR studies, It was found that sulphonamide pharmacophore preferred at meta-position of the phenyl ring, and that replacement the sulphonamide group of BPR1J-097 with the urea group resulted in a significant loss in cellular potency. Inhibition of FLT3 resulted in blockage of FLT3 and STAT5 phosphorylation and triggered apoptosis in cancer cells relying on FLT3 signalling for survival. In addition, BPR1J-097 showed favourable pharmacokinetic properties and significant dose dependent tumour reduction in FLT3-ITD murine xenograft models. These results demonstrate the potential of BPR1J-097 as a therapeutic candidate for treatment of AML patients. Further preclinical and clinical studies in AML patients are warranted. (source: Br J Cancer. 2012 Jan 31;106(3):475-81. doi: 10.1038/bjc.2011.564. Epub 2011 Dec 20.).
1: 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. BPR1J-097, a novel FLT3 kinase inhibitor, exerts potent inhibitory activity against AML. Br J Cancer. 2012 Jan 31;106(3):475-81. doi: 10.1038/bjc.2011.564. Epub 2011 Dec 20. PubMed PMID: 22187040; PubMed Central PMCID: PMC3273346.