BPR1J-097-Hydrochloride - FLT3 抑制劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBPR1J-097 HydrochlorideCat. No.: HY-13537A分式: CHClNOS分量: 553.08作靶點: FLT3作通路: Protein Tyrosine Kinase/RTK儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 6 mg/mL (10.85 mM; Need ultrasonic an

2、d warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.8081 mL 9.0403 mL 18.0806 mL5 mM 0.3616 mL 1.8081 mL 3.6161 mL10 mM 0.1808 mL 0.9040 mL 1.8081 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 BPR1J-097 Hydrochloride個新型且強效的 FLT3 抑制劑，其 IC50 值為 11 nM。IC50 & Target IC5

3、0: 11 nM (FLT3) 1體外研究BPR1J-097 Hydrochloride is a novel and potent FLT3 inhibitor with an IC50 of 11nM. Phosphorylation of allFLT3-WT, FLT3-IDT, and FLT3-D835Y are inhibited by BPR1J-097 Hydrochloride at a concentration as lowas 10nM. BPR1J-097 Hydrochloride suppresses the phosphorylation of FLT3 an

4、d STAT5 in a dose-dependent manner. The IC50 values of BPR1J-097 Hydrochloride on MOLM-13 and MV4-11 cells are 2171/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEand 4614 nM, respectively. The emergence of active caspase-3 is observed in MOLM-13 cells treated withBPR1J-097 Hydrochloride at 10nM. Th

5、e effect of BPR1J-097 Hydrochloride seems to be weaker in MV4-11cells as caspase-3 is not evident until 100nM of BPR1J-097 Hydrochloride is applied to treat cells 1.體內(nèi)研究 After i.v. administration of mice with BPR1J-097 Hydrochloride at two cycles of 10 or 25mg/kg, a clear dose-dependent anti-tumour

6、effect is observed. Tumours in mice treated with BPR1J-097 Hydrochloride (25mg/kgper day) stop growing. BPR1J-097 Hydrochloride (25mg/kg) shows a significant tumour shrinkage effect onthe subcutaneously growing MOLM-13 tumours in a size of 2000mm3. BPR1J-097 Hydrochloride (10 and25mg/kg) also produc

7、es a dose-dependent growth reduction and shrinkage of another model using MV4-11cells. It is noted that a prolonged disappearance of MV4-11 tumours is observed in mice treated with BPR1J-097 Hydrochloride at 25mg/kg. There is little (3%) or no body weight loss of BPR1J-097 Hydrochloride-treated nude

8、 mice during the observation periods in these in vivo studies 1.PROTOCOLKinase Assay 1 The FLT3 Kinase-Glo kinase assays are carried out in 96-well plates at 30C for 4h in a final volume of 50L, including 25 mM Tris pH 7.4, 10mM MgCl2, 4mM MnCl2, 1mM DTT, 0.02% Triton X-100, 0.01% BSA, 1M ATP, 20M p

9、eptide (GGMEDIYFEFMGGKKK), 75ng recombinant FLT3 proteins, and test compound(BPR1J-097) at the indicated concentration. After incubation, 50L Kinase-Glo Plus Reagent is added andincubated at 25C for 20min. A 70L aliquot of each reaction mixture is transferred to a black microtiter plateand the lumin

10、escence is measured on a multilabel counter. Each IC50 value is determined by three differentexperiments 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Proliferation assays are performed by seeding 10000 cells per well in a 96-well cultu

11、re plate. After 16h, cellsare then treated with vehicle or BPR1J-097 Hydrochloride at various concentrations in medium for 72h. Cellviability is quantitated using the MTS method. The results are determined by measuring absorbance at 490nm using a plate reader. The GC50 value is defined as the amount

12、 of compound that causes 50% reductionin cell viability in comparison with DMSO-treated (vehicle) control and is calculated using Prism version 4software 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male nude mice of 8 weeks of age are used.

13、 Nude mice (n=5 to 7 per group) are inoculated subcutaneouslyAdministration 1 with MOLM-13 (1106 per flank) or MV4-11 cells (5106 per flank). When the tumour size reaches 100 to200mm3, animals are grouped and treated with BPR1J-097 Hydrochloride at various doses in a 2-weektreatment period as indica

14、ted. Animals are treated with BPR1J-097 Hydrochloride (10 and 25mg/kg, i.v.) orvehicle as control at once daily for 5 days per week for 2 weeks. Tumour volumes are measured andcalculated with the formula lengthwidth2/2 after initiation of treatments. Tumour size and animal body weightare measured tw

15、ice a week after tumour cell inoculation. At the end of the study, animals are killed by carbondioxide inhalation followed by cervical dislocation 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Lin WH, et al. BPR1J-097, a novel FLT3 kinase inhibitor, exerts potent inhibitory activity against AML. Br J Ca