| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Colony-stimulating factor-1 receptor (CSF-1R / c-FMS), a tyrosine kinase receptor involved in macrophage differentiation, proliferation, and survival. c-Fms-IN-10 inhibits CSF-1R kinase activity by binding to the ATP-binding pocket of the receptor. It exhibits an IC50 of 2 nM against CSF-1R, demonstrating high potency and selectivity. The compound's thienopyrimidine core provides planar geometry for optimal binding to the kinase hinge region, with hydrogen bonding between the pyrimidine N1 and kinase residues.
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| ln Vitro |
In vitro studies demonstrate that c-Fms-IN-10 is a potent and selective inhibitor of CSF-1R with an IC50 of 2 nM. The compound effectively inhibits CSF-1R autophosphorylation and downstream signaling in cell-based assays. Its selectivity profile has been evaluated against other kinases, showing preferential inhibition of CSF-1R over related tyrosine kinases. The compound's anti-tumor activity has been validated in vitro, with studies demonstrating reduced proliferation and survival of CSF-1R-dependent cell lines. The thieno[3,2-d]pyrimidine scaffold was selected for its ability to occupy the ATP-binding pocket of c-FMS.
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| ln Vivo |
c-Fms-IN-10 has demonstrated anti-tumor activity in in vivo preclinical models. Studies in murine models have shown reduced tumor growth and metastasis following treatment with the compound. By inhibiting CSF-1R, the compound disrupts tumor-associated macrophage (TAM) proliferation and differentiation, thereby modulating the tumor immune microenvironment and reducing tumor progression. The compound's in vivo efficacy supports its potential as a therapeutic agent for solid tumors, particularly those with high TAM infiltration.
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| Enzyme Assay |
In vitro kinase assays for c-Fms-IN-10 measure inhibition of CSF-1R enzymatic activity. The assay is performed using recombinant human CSF-1R kinase domain and a peptide substrate in the presence of ATP. The compound is serially diluted in assay buffer and pre-incubated with the enzyme for 15-30 minutes. The reaction is initiated by adding ATP and substrate, and after incubation at 30degC for 30-60 minutes, phosphorylation is detected using either radiometric (33P-ATP) or non-radiometric (HTRF, AlphaScreen, or ELISA) methods. IC50 values are calculated from dose-response curves. Selectivity profiling against other kinases is performed using similar assays with appropriate substrates and ATP concentrations.
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| Cell Assay |
In vitro cell-based assays for c-Fms-IN-10 use cell lines that express CSF-1R, such as macrophage cell lines or CSF-1R-transfected cells. Cells are cultured in appropriate media and treated with varying concentrations of the compound for 2-6 hours. CSF-1R autophosphorylation is assessed by Western blotting using phospho-specific antibodies (e.g., anti-phospho-CSF-1R). Downstream signaling (ERK, Akt phosphorylation) is also evaluated. Cell proliferation is measured using MTT or BrdU incorporation assays. The compound's effect on macrophage differentiation and survival is assessed in CSF-1-dependent cell lines.
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| Animal Protocol |
In vivo animal studies for c-Fms-IN-10 are conducted in murine tumor models. A typical protocol involves subcutaneous implantation of tumor cells (e.g., syngeneic or xenograft models) in immunocompetent or immunodeficient mice. When tumors reach a certain size, animals are randomized to receive vehicle control or c-Fms-IN-10 at doses of 1-30 mg/kg via oral or intraperitoneal administration, daily or twice daily. Tumor volumes are measured with calipers every 2-3 days. Tumor tissues are analyzed for CSF-1R phosphorylation, TAM infiltration (F4/80, CD68 staining), and markers of proliferation (Ki-67) and apoptosis (TUNEL). Plasma samples are collected for pharmacokinetic analysis.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of c-Fms-IN-10 are characteristic of small-molecule kinase inhibitors. The compound has a molecular weight of 429.50 and is soluble in DMSO at 10 mg/mL (23.28 mM). It is typically formulated in DMSO for in vitro studies and in suitable vehicles (e.g., PEG400, saline, or cyclodextrin-based formulations) for in vivo administration. The compound is stored at -20degC in a desiccated environment to maintain stability. Standard pharmacokinetic parameters (clearance, volume of distribution, half-life, oral bioavailability) can be determined following intravenous and oral administration in preclinical species.
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| Toxicity/Toxicokinetics |
As a research-use kinase inhibitor, comprehensive toxicity data for c-Fms-IN-10 are primarily derived from preclinical studies. The compound is intended for research purposes only and not for human therapeutic use. Standard safety precautions for handling chemical compounds apply, including the use of appropriate personal protective equipment. Acute and chronic toxicity studies have not been extensively reported in the literature for this specific compound. The compound's safety profile is evaluated in the context of in vivo efficacy studies, where body weight, clinical signs, and histopathological findings are monitored.
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| References | |
| Additional Infomation |
c-Fms-IN-10 is a research-grade thieno[3,2-d]pyrimidine derivative and potent CSF-1R kinase inhibitor. It is classified as a kinase inhibitor targeting the FMS/CSF-1R pathway with an IC50 of 2 nM. The compound has demonstrated anti-tumor activity in preclinical models. Its chemical name is 4-amino-N-{3-methyl-1-[(6-methylpyridin-2-yl)methyl]-1H-indazol-4-yl}thieno[3,2-d]pyrimidine-6-carboxamide. Purity is ≥98% by HPLC. The compound is used as a research tool for studying CSF-1R biology, tumor-associated macrophages, and cancer immunotherapy. Not approved for clinical use.
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| Molecular Formula |
C22H19N7OS
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|---|---|
| Molecular Weight |
429.4976
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| Exact Mass |
429.137
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| CAS # |
1527517-50-5
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| PubChem CID |
72943374
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
653
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C([H])=C(C2=C1C(N([H])[H])=NC([H])=N2)C(N([H])C1C([H])=C([H])C([H])=C2C=1C(C([H])([H])[H])=NN2C([H])([H])C1=C([H])C([H])=C([H])C(C([H])([H])[H])=N1)=O
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| InChi Key |
KZVIZFHCMVWFNT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H19N7OS/c1-12-5-3-6-14(26-12)9-29-17-8-4-7-16(18(17)13(2)28-29)27-22(30)15-10-31-20-19(15)24-11-25-21(20)23/h3-8,10-11H,9H2,1-2H3,(H,27,30)(H2,23,24,25)
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| Chemical Name |
4-amino-N-[3-methyl-1-[(6-methylpyridin-2-yl)methyl]indazol-4-yl]thieno[3,2-d]pyrimidine-7-carboxamide
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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 (~23.28 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1 mg/mL (2.33 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 1 mg/mL (2.33 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3283 mL | 11.6414 mL | 23.2829 mL | |
| 5 mM | 0.4657 mL | 2.3283 mL | 4.6566 mL | |
| 10 mM | 0.2328 mL | 1.1641 mL | 2.3283 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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