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BPR1J-097 Hydrochloride is a novel and potent FLT3 inhibitor with an IC₅₀ of 11 nM.

BPR1J-097 Hydrochloride is a novel and potent FLT3 inhibitor with an IC₅₀ of 11nM. Phosphorylation of all FLT3-WT, FLT3-IDT, and FLT3-D835Y are inhibited by BPR1J-097 Hydrochloride at a concentration as low as 10 nM. BPR1J-097 Hydrochloride suppresses the phosphorylation of FLT3 and STAT5 in a dose-dependent manner. The IC₅₀ values of BPR1J-097 Hydrochloride on MOLM-13 and MV4-11 cells are 21±7 and 46±14 nM, respectively. The emergence of active caspase-3 is observed in MOLM-13 cells treated with BPR1J-097 Hydrochloride at 10 nM. The effect of BPR1J-097 Hydrochloride seems to be weaker in MV4-11 cells as caspase-3 is not evident until 100 nM of BPR1J-097 Hydrochloride is applied to treat cells.

After i.v. administration of mice with BPR1J-097 Hydrochloride at two cycles of 10 or 25 mg/kg, a clear dose-dependent anti-tumour effect is observed. Tumours in mice treated with BPR1J-097 Hydrochloride (25 mg/kg per day) stop growing. BPR1J-097 Hydrochloride (25 mg/kg) shows a significant tumour shrinkage effect on the subcutaneously growing MOLM-13 tumours in a size of >2000 mm. BPR1J-097 Hydrochloride (10 and 25 mg/kg) also produces 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 is observed in mice treated with BPR1J-097 Hydrochloride at 25 mg/kg. There is little (3%) or no body weight loss of BPR1J-097 Hydrochloride-treated nude mice during the observation periods in these in vivo studies.

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