BPR1R024 mesylate is a selective, orally bioactive, colony-stimulating factor-1 receptor (CSF1R) inhibitor. BPR1R024 mesylate is the equivalent of BPR1R024. BPR1R024 has potent CSF1R inhibitory activity with IC50 of 0.53 nM. BPR1R024 may be used in immuno-oncology research.

Physicochemical Properties

Molecular Formula	C25H25F3N6O5S
Molecular Weight	578.56
Exact Mass	578.155
CAS #	2763365-40-6
Related CAS #	BPR1R024;2503015-75-4
PubChem CID	164621161
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	6
Heavy Atom Count	40
Complexity	781
Defined Atom Stereocenter Count	0
InChi Key	IOTHUERMMPFCSD-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H21F3N6O2.CH4O3S/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;1-5(2,3)4/h3-12,14H,13H2,1-2H3,(H2,29,32,34);1H3,(H,2,3,4)
Chemical Name	1-[4-[7-(dimethylamino)quinazolin-4-yl]oxyphenyl]-3-[[6-(trifluoromethyl)pyridin-3-yl]methyl]urea;methanesulfonic acid
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

Targets	IC50: 0.53 nM (CSF1R); 10 μM (AURA); 1.40 μM (AURB)[1].
ln Vitro	BPR1R024 (compound 12) exhibits a strong inhibitory effect on CSF1R, with an IC50 of 0.53 nM [1]. The CSF1R signal was markedly decreased in a dose-dependent manner by (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) selectively suppresses the proliferation of anticancer M1-like macrophages while having little effect on protumor M2-like macrophage survival[1].
ln Vivo	In a mouse colon tumor model, BPR1R024 (compound 12) (oral; 100 mg/kg; twice a day) demonstrates anticancer and immunomodulatory activity[1].
Cell Assay	Western Blot Analysis[1] Cell Types: RAW264.7 and THP-1 cells Tested Concentrations: 0-500 nM Incubation Duration: 16 h Experimental Results: Dramatically suppressed the CSF1R signal in a dose-dependent manner, at concentrations of approximately 50-75 and 1-10 nM in RAW264.7 and THP-1 cells, respectively.
Animal Protocol	Animal/Disease Models: Rats[1] Doses: 5, 20, 25 mg/kg Route of Administration: IV, PO Experimental Results: demonstrated high systemic drug exposure with the dose-normalized area under curve (DNAUC) values of 3635 ng/mL*h by the IV route and 362 ng/mL*h by the PO route and the modification increased oral bioavailability (F=35%). Animal/Disease Models: C57BL/6 mice (sixweeks old, male)[1] Doses: 100 mg/kg Route of Administration: po (oral gavage) twice a day Experimental Results: Delayed the MC38 murine colon tumor growth and reversed the immunosuppressive tumor microenvironment with the increased 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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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	1.7284 mL	8.6421 mL	17.2843 mL
	5 mM	0.3457 mL	1.7284 mL	3.4569 mL
	10 mM	0.1728 mL	0.8642 mL	1.7284 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.