WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 401161
CAS#: 1327167-19-0
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 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.
MedKoo Cat#: 401161
Name: BPR1J-097
CAS#: 1327167-19-0
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
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | An FLT3 inhibitor. |
| In vitro activity: | BPR1J-097 is a novel compound with a novel sulphonamide pharmacophore (Figure 1). BPR1J-097 exhibits potent FLT3-inhibitory activity and has potent growth-inhibitory effects on FLT3-ITD leukaemic cells. As shown in Table 1, BPR1J-097 potently inhibited wild-type FLT3 (FLT3-WT) activity with an IC50 of 11±7 n. BPR1J-097 specifically targets FLT3 kinase with weaker inhibitory activity towards related kinases such as FLT1 (VEGFR1) and KDR (VEGFR2) (Table 2). In a screening assay for kinase inhibition specificity, 59%, and 91% of FLT1 and KDR activities, respectively, were inhibited by BPR1J-097 at 1 μ. Reference: Br J Cancer. 2012 Jan 31; 106(3): 475–481. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273346/ |
| In vivo activity: | In contrast to ABT-869, BPR1J-097 (25 mg kg−1) showed a significant tumour shrinkage effect on the subcutaneously growing MOLM-13 tumours in a size of >2000 mm3 (Figure 5B). Tumours started to grow after the termination of BPR1J-097 treatment. Compared with ABT-869, BPR1J-097 seemed to be more efficacious in the MOLM-13 xenograft model. Furthermore, BPR1J-097 (10 and 25 mg kg−1) also produced a dose-dependent growth reduction and shrinkage of another model using MV4-11 cells. It is noted that a prolonged disappearance of MV4-11 tumours was observed in mice treated with BPR1J-097 at 25 mg kg−1 (Figure 5C). There was little (3%) or no body weight loss of BPR1J-097-treated nude mice during the observation periods in these in vivo studies. It is interesting to note that although BPR1J-097 was able to trigger more apoptosis in MOLM-13 cells than in MV4-11 cells (Figure 3A), BPR1J-097 seemed more effective for MV4-11 than for MOLM-13 xenograft tumours (Figure 5C). Reference: Br J Cancer. 2012 Jan 31; 106(3): 475–481. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273346/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 10.0 | 19.36 | |
| DMF | 30.0 | 58.07 | |
| DMF:PBS (pH 7.2) (1:6) | 0.14 | 0.27 |
The following data is based on the product molecular weight 516.61 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 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. PMID: 22187040; PMCID: PMC3273346. |
| In vitro protocol: | 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. PMID: 22187040; PMCID: PMC3273346. |
| In vivo protocol: | 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. PMID: 22187040; PMCID: PMC3273346. |
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.
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.).
