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| Targets |
IC50: 11 nM (FLT3)[1]
BPR1J-097 Hydrochloride targets the FMS-like tyrosine kinase 3 (FLT3), a receptor tyrosine kinase that is important for normal hematopoiesis and is often dysregulated in acute myeloid leukemia (AML) [24L20-L21]. It is a Type I, ATP-competitive inhibitor that binds to the active conformation of FLT3 [24L13-L14]. The compound potently inhibits both the wild-type (FLT3-WT) and the most common clinically relevant mutants, including internal tandem duplication (FLT3-ITD) and point mutations like the tyrosine kinase domain mutation D835Y (FLT3-D835Y) [24L6-L8]. |
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| ln Vitro |
BPR1J-097 Hydrochloride is a new, powerful FLT3 inhibitor with an 11nM IC50. BPR1J-097 Hydrochloride inhibits FLT3-phosphorylation-WT, FLT3-IDT, and FLT3-D835Y at concentrations as low as 10 nM. In a dose-dependent manner, BPR1J- 097 Hydrochloride inhibits the phosphorylation of FLT3 and STAT5. On MOLM-13 and MV4-11 cells, the IC50 values of BPR1J-097 Hydrochloride are 21±7 and 46±14 nM, respectively. Following treatment with BPR1J-097 Hydrochloride at a concentration of 10 nM, MOLM-13 cells exhibit the appearance of activated caspase-3. Since caspase-3 is not seen until 100 nM of BPR1J-097 Hydrochloride is administered to treat cells, the effect of the hydrochloride appears to be reduced in MV4-11 cells[1].
In vitro, BPR1J-097 Hydrochloride is a potent FLT3 inhibitor with an IC₅0 of 11 nM [24L5-L6]. It effectively inhibits the phosphorylation of FLT3-WT, FLT3-ITD, and the FLT3-D835Y mutant at concentrations as low as 10 nM [24L6-L8]. In cell proliferation assays using human AML cell lines, the compound shows potent anti-proliferative effects, with IC₅0 values of 21+/-7 nM and 46+/-14 nM against FLT3-ITD-positive MOLM-13 and FLT3-WT MV4-11 cells, respectively [26L28-L30]. It also induces apoptosis, as evidenced by the appearance of active caspase-3 in MOLM-13 cells at 10 nM [26L30-L32]. |
| ln Vivo |
Mice given BPR1J-097 Hydrochloride intravenously (IV) for two cycles at 10 or 25 mg/kg, a definite dose-dependent antitumor effect is seen. When mice are given BPR1J-097 Hydrochloride (25 mg/kg daily), their tumors stop developing. When BPR1J-097 Hydrochloride (25 mg/kg) is applied topically to subcutaneously developing MOLM-13 tumors larger than 2000 mm3, there is a noticeable reduction in tumor size. Using MV4-11 cells, BPR1J-097 Hydrochloride (10 and 25 mg/kg) also causes a dose-dependent shrinkage and reduction in growth of another model. It is reported that mice given 25 mg/kg of BPR1J-097 Hydrochloride showed a prolonged elimination of MV4-11 tumors. In these in vivo experiments, BPR1J-097 Hydrochloride-treated nude mice lose little (3%), if any, of their body weight during the observation periods[1].
In vivo, BPR1J-097 Hydrochloride demonstrates significant anti-tumor activity in xenograft mouse models of AML. After intravenous administration at doses of 10 or 25 mg/kg (two cycles), a clear dose-dependent anti-tumor effect is observed [26L34-L36]. At a dose of 25 mg/kg per day, tumor growth is stopped, and in mice with large MOLM-13 tumors (>2000 mm3), a significant tumor shrinkage effect is observed [26L36-L39]. These data support the potent in vivo efficacy of this FLT3 inhibitor. |
| Enzyme Assay |
BPR1J-097's binding to FLT3 is assessed using standard cell-free kinase inhibition assays. In this protocol, purified recombinant FLT3 kinase is incubated with varying concentrations of BPR1J-097, along with ATP and a specific peptide substrate. The kinase activity is measured by quantifying the amount of phosphorylated product, typically using an ADP-Glo luminescence assay or by detecting 32P incorporation into the substrate. The half-maximal inhibitory concentration (IC₅0) value is derived from a dose-response curve, confirming an 11 nM value [24L5-L6].
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| Cell Assay |
For cellular assays, human AML cell lines (MOLM-13 with FLT3-ITD or MV4-11 with FLT3-WT) are used. Cells are treated with various concentrations of BPR1J-097 (e.g., 1-1000 nM) for 2-4 hours. The cells are then lysed, and the levels of phosphorylated FLT3 (p-FLT3) and its downstream signaling proteins, such as phosphorylated STAT5 (p-STAT5) and ERK (p-ERK), are measured by Western blot. The IC₅0 for inhibiting these phosphorylation events is calculated. For anti-proliferation assays, cells are treated for 48-96 hours, and viability is measured by MTT or CellTiter-Glo.
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| Animal Protocol |
In vivo studies are performed in a mouse xenograft model of AML using the MOLM-13 cell line (FLT3-ITD positive). 5-6 week old female severe combined immunodeficiency (SCID) or NOD/SCID mice are injected subcutaneously with MOLM-13 cells. Once tumors reach a palpable size (e.g., 100-150 mm3), the mice are randomized and treated with BPR1J-097 Hydrochloride. The compound is administered intravenously (i.v.) at doses of 10 or 25 mg/kg, typically daily for two cycles [26L34-L35]. Tumor volume is measured every 2-3 days using calipers. At the end of the study, tumors are excised, weighed, and analyzed for p-FLT3 and other biomarkers.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for BPR1J-097 Hydrochloride are not detailed in standard product literature. However, the in vivo efficacy studies demonstrated that the compound is active via the intravenous (i.v.) route, indicating that it is systemically available [26L34-L35]. The effective doses of 10-25 mg/kg i.v. suggest a manageable clearance rate. Further PK studies would be required to determine its half-life, volume of distribution, and oral bioavailability.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for BPR1J-097 Hydrochloride are not detailed in standard product documentation. As a potent FLT3 inhibitor, potential on-target toxicities may include myelosuppression (neutropenia, anemia, thrombocytopenia), gastrointestinal issues, and off-target toxicities related to other kinases it may inhibit. In the in vivo efficacy studies, no significant adverse events or weight loss in the animals were reported at the tested doses. For research use, standard chemical safety precautions for kinase inhibitors should be followed.
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| References | |
| Additional Infomation |
BPR1J-097 Hydrochloride has the molecular formula C2₇H2₉ClN₆O3S and a molecular weight of 553.08 g/mol [25L6-L7]. The free base CAS number is 1327167-19-0 [25L8]. It appears as a white to off-white solid powder [25L8-L9]. The compound has a purity of ≥98%. The powder is stable for up to 3 years at -20degC, and solutions can be stored at -80degC for 6 months [25L10-L12]. It is slightly soluble in DMSO (<6 mg/mL) and water (<2 mg/mL) [25L16-L18].
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| Molecular Formula |
C27H29CLN6O3S
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| Molecular Weight |
553.08
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| Related CAS # |
BPR1J-097;1327167-19-0
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~6 mg/mL (~10.85 mM)
H2O :~2 mg/mL (~3.62 mM) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8081 mL | 9.0403 mL | 18.0806 mL | |
| 5 mM | 0.3616 mL | 1.8081 mL | 3.6161 mL | |
| 10 mM | 0.1808 mL | 0.9040 mL | 1.8081 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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