Physicochemical Properties
| Molecular Formula | C24H21F3N6O2 |
| Molecular Weight | 482.46 |
| Exact Mass | 482.167 |
| CAS # | 2503015-75-4 |
| Related CAS # | BPR1R024 mesylate;2763365-40-6 |
| PubChem CID | 155195529 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 3.9 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 35 |
| Complexity | 689 |
| Defined Atom Stereocenter Count | 0 |
| 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 |
| InChi Key | ORYMWWSJZRCUSV-UHFFFAOYSA-N |
| 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) |
| Chemical Name | 1-[4-[7-(dimethylamino)quinazolin-4-yl]oxyphenyl]-3-[[6-(trifluoromethyl)pyridin-3-yl]methyl]urea |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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]. |
| ln Vivo | BPR1R024 (Compound 12) (orally; 100 mg/kg; twice daily) displays anticancer and immunomodulatory effects in a mouse colon tumor model [1]. |
| 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. |
| 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. |
| References |
[1]. Discovery of BPR1R024, an Orally Active and Selective CSF1R Inhibitor that Exhibits Antitumor and Immunomodulatory Activity in a Murine Colon Tumor Model. J Med Chem. 2021 Oct 14;64(19):14477-14497. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~10 mg/mL (~20.73 mM) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |