| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
The compound specifically targets the tyrosine kinase receptor CSF1R. By inhibiting CSF1R, BPR1R024 disrupts the signaling pathway that is essential for the survival, proliferation, and differentiation of tumor-associated macrophages (TAMs), particularly the pro-tumorigenic M2-like macrophages, while sparing the anti-tumorigenic M1-like macrophages, thereby modulating the tumor microenvironment.
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| ln Vitro |
BPR1R024 (compound 12) exhibits a strong inhibitory effect on CSF1R, with an IC50 of 0.53 nM [1]. With IC50 values >10 μM and 1.40 μM, respectively, BPR1R024 demonstrated mild inhibitory effects against AURA and AURB in the enzyme activity assay [1]. CSF1R signaling is markedly and dose-dependently inhibited by BPR1R024 (0-500 nM) [1]. TNF-α production mediated by CSF1/CSF1R signaling is inhibited by BPR1R024 (10 nM, 100 nM) [1]. BPR1R024 (0–10 μM) mostly suppresses pro-tumor M2-like macrophage proliferation while having little effect on anti-tumor M1-like macrophage growth [1].
In enzyme assays, BPR1R024 exhibits an IC50 of 0.53 nM for CSF1R, with weaker activity against Aurora A (IC50 >10 uM) and Aurora B (IC50 1.40 uM), confirming its selectivity. In cellular assays, it significantly suppresses the CSF1R signal in a dose-dependent manner. At 10 nM and 100 nM, the compound inhibits TNF-alpha production mediated by the CSF1/CSF1R signaling pathway and specifically inhibits the survival of M2-like macrophages. |
| ln Vivo |
BPR1R024 (Compound 12) (orally; 100 mg/kg; twice daily) displays anticancer and immunomodulatory effects in a mouse colon tumor model [1].
BPR1R024 exhibits antitumor and immunomodulatory activity in a murine colon tumor model when administered orally. The compound is evaluated for its ability to modulate the tumor immune microenvironment, for example, by reducing the number of immunosuppressive M2-like TAMs and increasing the proportion of CD8+ T cells, leading to tumor growth inhibition. A typical in vivo efficacy study involves a syngeneic mouse model such as MC38 colon adenocarcinoma. The assay involves incubating purified CSF1R kinase with a biotinylated substrate peptide and ATP in the presence of varying concentrations of BPR1R024. After the reaction, the amount of phosphorylated peptide is detected using a time-resolved fluorescence resonance energy transfer (TR-FRET) method to calculate the IC50. |
| Enzyme Assay |
For cellular assays, RAW264.7 (mouse macrophage) or THP-1 (human monocyte) cells are used. Cells are treated with various concentrations of BPR1R024 (0-500 nM). After 16 hours of incubation, cells are stimulated with CSF-1 (the ligand for CSF1R). The cells are then lysed, and the phosphorylation of CSF1R or its downstream signaling proteins (e.g., ERK) is analyzed by Western blot using phospho-specific antibodies. The concentration at which CSF1R signaling is reduced by 50% is determined.
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| Cell Assay |
Western blot analysis[1]
Cell Types: RAW264.7 and THP-1 Cell Tested Concentrations: 0-500 nM Incubation Duration: 16 hrs (hours) Experimental Results: Concentrations are approximately 50-75 and 1- in RAW264.7 and THP-1 cells respectively 10 nM. In a murine MC38 colon adenocarcinoma model, female C57BL/6 mice bearing subcutaneous tumors (~100 mm3) are randomized into groups. BPR1R024 is administered orally at a dose of 100 mg/kg twice daily. Tumor growth is monitored by caliper measurement. Upon study termination, tumors are excised and analyzed by flow cytometry for immune cell populations (e.g., M1 vs. M2 macrophages, CD8+ T cells) and by immunohistochemistry for CSF1R pathway markers. |
| Animal Protocol |
Animal/Disease Models: Rat[1]
Doses: 5, 20, 25 mg/kg Route of Administration: intravenous (iv) (iv)injection, oral administration Experimental Results: demonstrated high systemic drug exposure, with an area under the dose normalized curve (DNAUC) value of 3635 ng/mL*h IV route and PO route 362 ng/mL*h and modification increased oral bioavailability (F=35%). Animal/Disease Models: C57BL/6 mice (six weeks old, male) [1] Doses: 100 mg/kg Doses: po (po (oral gavage)) twice (two times) daily Experimental Results: Delayed the growth of colon tumors in MC38 mice and reversed immunosuppressive tumor microarray environment. M1/M2 ratio. BPR1R024 is orally bioavailable. Specific PK parameters are provided for a study in rats: after oral administration at 25 mg/kg, the Cmax (maximum plasma concentration) was 0.11 microg/mL, and the oral bioavailability (F%) was 1.4%, indicating limited absorption. After intravenous administration at 5 mg/kg, the compound exhibited a high clearance (CL) of 2.17 L/h/kg and a volume of distribution at steady state (Vdss) of 2.34 L/kg. |
| ADME/Pharmacokinetics |
Specific toxicological data for BPR1R024 are not detailed in the available literature. As a selective CSF1R inhibitor, its primary on-target toxicity profile might include effects on macrophage populations in normal tissues. However, its selectivity profile suggests it may have an improved safety window compared to less selective kinase inhibitors. Standard in vivo toxicological endpoints would include body weight monitoring and histopathological analysis.
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| Toxicity/Toxicokinetics |
BPR1R024 is a research-grade chemical that has been identified as a potent and selective tool for studying CSF1R biology in the tumor microenvironment. It demonstrates that selective depletion of M2-like TAMs is a viable strategy for cancer immunotherapy. As of the latest updates, this compound is in the pre-clinical research phase and has not been approved for clinical use.
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| References |
| Molecular Formula |
C24H21F3N6O2
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|---|---|
| Molecular Weight |
482.46
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| Exact Mass |
482.167
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| CAS # |
2503015-75-4
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| Related CAS # |
BPR1R024 mesylate;2763365-40-6
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| PubChem CID |
155195529
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
689
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=NC=C(CNC(=O)NC2=CC=C(C=C2)OC2=NC=NC3=CC(N(C)C)=CC=C23)C=C1)C(F)(F)F
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| InChi Key |
ORYMWWSJZRCUSV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H21F3N6O2/c1-33(2)17-6-9-19-20(11-17)30-14-31-22(19)35-18-7-4-16(5-8-18)32-23(34)29-13-15-3-10-21(28-12-15)24(25,26)27/h3-12,14H,13H2,1-2H3,(H2,29,32,34)
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| Chemical Name |
1-[4-[7-(dimethylamino)quinazolin-4-yl]oxyphenyl]-3-[[6-(trifluoromethyl)pyridin-3-yl]methyl]urea
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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 |
| 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 : ~10 mg/mL (~20.73 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 | 2.0727 mL | 10.3636 mL | 20.7271 mL | |
| 5 mM | 0.4145 mL | 2.0727 mL | 4.1454 mL | |
| 10 mM | 0.2073 mL | 1.0364 mL | 2.0727 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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